Case#: Subject number 27(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 108 U/L (60-305 U/L is normal), AST: 32 U/L (22-71 U/L is normal), ALT: 29 U/L (7-50 U/L is normal), Hex4: 3.3 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 35.7 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 (NBS) is 1.1 micromole/L/h and GAA activity #2 (NBS) 0.42 in dried blood spots (>2.10 micromole/L/h is normal). 2.40 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.1441T>C

Variant 1 ClinVarID: 189007

Variant 1 CAid: CA274247

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 15(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 68 U/L (60-305 U/L is normal), AST: 49 U/L (20-64 U/L is normal), ALT: 27 U/L (12-42 U/L is normal), Hex4: 2.8 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.11 micromole/L/h and GAA activity #2 (NBS) 0.5 in dried blood spots (>2.10 micromole/L/h is normal). 1.60 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.-32-13T>G

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 24(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 197 U/L (60-305 U/L is normal)

glucosidase activity: GAA activity #2 (NBS) 0.43 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.1856G>A

Variant 1 ClinVarID: 370146

Variant 1 CAid: CA8815500

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 21(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 155 U/L (60-305 U/L is normal), AST: 71 U/L (22-71 U/L is normal), ALT: 60 U/L (7-50 U/L is normal), Hex4 12.6 mmol/mol Creatine (≤20 is normal)

glucosidase activity: GAA activity #1 was 1.77 micromole/L/h and GAA activity #2 (NBS) 0.84 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.-32-13T>G

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 19(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 510 U/L (60-305 U/L is normal), AST: 158 U/L (22-71 U/L is normal), ALT: 39 U/L (7-50 U/L is normal), Hex4: 8.1 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP <10.0 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.07 micromole/L/h and GAA activity #2 (NBS) 0.38 in dried blood spots (>2.10 micromole/L/h is normal). 1.10 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.456_458insGA

Variant 1 ClinVarID: ?

Variant 1 CAid: ?

Variant 2: NM_000152.5(GAA):c.-32-13T>G

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 542 U/L (60-305 U/L is normal), AST: 152 U/L (22-71 U/L is normal), ALT: 55 U/L (7-50 U/L is normal), Hex4: 7.6 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 16.5 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.7 micromole/L/h and GAA activity #2 (NBS) 0.34 in dried blood spots (>2.10 micromole/L/h is normal). 1.40 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2560C>T

Variant 2 ClinVarID: 4034

Variant 2 CAid: CA340130

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 145 U/L (60-305 U/L is normal), AST: 72 U/L (22-71 U/L is normal), ALT: 43 U/L (7-50 U/L is normal), Hex4: 5.3 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 13.0 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.97 micromole/L/h and GAA activity #2 (NBS) 0.33 in dried blood spots (>2.10 micromole/L/h is normal). 0.93 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.2281delGinsAT

Variant 2 ClinVarID: 370993

Variant 2 CAid: CA16041905

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case13: Male, 5 yr onset, 2 yr diagnosis, 7.6 yr report

HPOsFreeText: Respiratory support at night, FVC z-score sitting -1.77 (78% pred), FVC z-score supine -1.72 (79% pred), 100% MRC Scale, 436 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used

CaseA1: 26 years onset

CaseAddInfo: Late-Onset Pompe Disease, Sibling of A2

Variant: NM_000152.4:c.1212C>G (p.Asp404Glu)

CAID: CA401365194 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.1212C%3EG

gnomAD: Not in gnomAD

VariantAddInfo: This variant was declared as novel and found in a patient, but no further information was given.

Case22: Male, 16 years onset, 41 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Variant: NM_000152.4:c.2109del (p.Tyr703Ter)

CAID: CA891862616 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.2109del

gnomAD: Not in gnomAD

VariantAddInfo: This variant was declared as novel and found in a patient, but no further information was given.

Case13: Male, 9 years onset, 19 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case#: Patient 4

DiseaseAssertion: Pompe Disease

FamilyInfo: None given

CasePresentingHPOs: None

CaseHPOFreeText: None

CaseNotHPOs: None

CaseNotHPOFreeText: None

CasePreviousTesting: Single gene sequencing with Ion Torrent Persional Genome Machine

Glucosidase activity: 0.0 nmol 5MU/hr/mL

Variant 1: NM_000152.5:c.596A>G

Variant 1 ClinVarID: 92486

Variant 1 CAid: CA145785

Variant 2: NM_000152.5:c.668G>A

Variant 2 ClinVarID: 92488

Variant 2 CAid: CA145791

ParentalGenotype: Not provided

Case#: Patient 8

DiseaseAssertion: Pompe Disease

FamilyInfo: None given

CasePresentingHPOs: None

CaseHPOFreeText: None

CaseNotHPOs: None

CaseNotHPOFreeText: None

CasePreviousTesting: Single gene sequencing with Ion Torrent Persional Genome Machine

Glucosidase activity: 0.05 nmol 5MU/hr/mL

Variant 1: NM_000152.5:c.596A>G

Variant 1 ClinVarID: 92486

Variant 1 CAid: CA145785

Variant 2: NM_000152.5:c.472A>G

Variant 2 ClinVarID:

Variant 2 CAid: CA401361595

Variant 3: NM_000152.5:c.668G>A

Variant 3 ClinVarID: 92488

Variant 3 CAid: CA145791

Variant 4: NM_000152.5:c.503G>T

Variant 4 ClinVarID:

Variant 4 CAid: CA8814883

ParentalGenotype: Not provided

Case#: Patient 5

DiseaseAssertion: Pompe Disease

FamilyInfo: None given

CasePresentingHPOs: None

CaseHPOFreeText: None

CaseNotHPOs: None

CaseNotHPOFreeText: None

CasePreviousTesting: Single gene sequencing with Ion Torrent Persional Genome Machine

Glucosidase activity: 0.0 nmol 5MU/hr/mL

Variant 1: NM_000152.5:c.2560C>T

Variant 1 ClinVarID: 4034

Variant 1 CAid: CA340130

Variant 2: NM_000152.5:c.2446G>A

Variant 2 ClinVarID: 92477

Variant 2 CAid: CA145772

ParentalGenotype: Not provided

Case#: Patient 7

DiseaseAssertion: Pompe Disease

FamilyInfo: None given

CasePresentingHPOs: None

CaseHPOFreeText: None

CaseNotHPOs: None

CaseNotHPOFreeText: None

CasePreviousTesting: Single gene sequencing with Ion Torrent Persional Genome Machine

Glucosidase activity: 0.05 nmol 5MU/hr/mL

Variant 1: NM_000152.5:c.2560C>T

Variant 1 ClinVarID: 4034

Variant 1 CAid: CA340130

Variant 2: NM_000152.5:c.596A>G

Variant 2 ClinVarID: 92486

Variant 2 CAid: CA145785

Variant 3: NM_000152.5:c.668G>A

Variant 3 ClinVarID: 92488

Variant 3 CAid: CA145791

ParentalGenotype: Not provided

Patient9: Male, <1 year onset

CaseAddInfo: LOPD

Patient7: Female, 1 year onset

CasePresentingHPOs: HP:0002240 (Hepatomegaly)

HPOsFreeText: GAA activity 1% from leukocyte

CaseNotHPOs: HP:0002098, HP:0001324, HP:0001640 (Respiratory distress, Muscle weakness, Cardiomegaly)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: LOPD

Patient3: Female, 6 years report, birth onset

CasePresentingHPOs: HP:0001640, HP:0002240, HP:0001324 (Cardiomegaly, Hepatomegaly, Muscle weakness)

HPOsFreeText: GAA activity 2.1% from leukocyte

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: IOPD

Case6: Female, French, 26 years report, 21 years onset

CasePresentingHPOs: HP:0008956 (Thigh muscle atrophy)

HPOsFreeText: 6-min walk test achieved 496 m, MRC score is 3/5 (thigh/calf), Forced vital capacity sitting/supine is 2.2/1.9 (L), Has started ERT,On the medication Perindopril

GroupGenotypingMethod: Mutation Analysis on the GAA Gene

Variant1: NM_000152.4:c.-32-13T>A

CAID: CA913184742 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184742

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.525delT (p.Glu176Argfs)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Patient35: male, Caucasian

CasePresentingHPOs: HP:0003676, HP:0003236, HP:0003325, HP:0008994, HP:0003458, HP:0003560, HP:0030121

HPOsFreeText: CK < 10x increase, difficulty ascending stairs, inability to stand without aid, treated with ERT

CaseNotHPOs: HP:0002093

CaseAddInfo: onset as young adult. Older sister also affected with onset at 21 yo. She now exhibits scoliosis, fatigability, paraspinal muscle atrophy, proximal upper limp atrophy, and weakness. Calpain deficiency detected via immunoblot could be connected to CAPN3 variants (p.Gly333Asp [c.998G > A] and p.Ala726Ser [c.2176G > T]).

CasePreviousTesting: same as group, EMG, muscle biopsy, immunoblot analysis

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.569G>A (p.Arg190His)

ClinVar: 188809, https://www.ncbi.nlm.nih.gov/clinvar/variation/188809/

gnomAD: 8.276e-06, http://exac.broadinstitute.org/variant/17-78079570-G-A

Variant2: NM_000152.3:c.2020C>G

CAID: CA401370092, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401370092

gnomAD: n/a

CaseOPOPD-11: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.98 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.701C>T (p.Thr234Met)

ClinVar: CA8814994 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.701C%3ET

gnomAD: South Asian 3.266e-5, Overall 1.196e-5 http://gnomad.broadinstitute.org/variant/17-78081364-C-T

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation and One Pseudodeficency Mutation

CaseLP-1: Female, Taiwan, Birth diagnosis

HPOsFreeText: 4MU enzyme activity at 0.44, MS/MS ennzyme activity at 0.08

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.3:c.424_440del (p.Ser142Leufs*29)

CAID: CA658795228 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.424_440del17

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1958C>A (p.Thr653Asn)

CAID: CA8815557 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1958C%3EA

gnomAD: East Asian 2.548e-4, Overall 1.825e-5 http://gnomad.broadinstitute.org/variant/17-78086744-C-A

CaseAddInfo: Suspected Late Onset Pompe Disease

CaseIP2-2: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.09 umol/hr/L, Serum CK at 458 U/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.872T>C (p.Leu291Pro)

CAID: CA401363854 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.872T%3EC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant3: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature indicates Variant 1 and 2 are in trans, also that Variant 3 is in cis with only one of them

CaseLP-2: Female, Taiwan, Birth diagnosis

HPOsFreeText: 4MU enzyme activity at 0.85, MS/MS ennzyme activity at 0.42

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.671G>A (p.Arg224Gln)

CAID: CA8814958 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.671G%3EA

gnomAD: African 8.060e-5, Overall 2.549e-5 http://gnomad.broadinstitute.org/variant/17-78079672-G-A

Variant2: NM_000152.4:c.752C>T (p.Ser251Leu)

ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T

Variant3: NM_000152.4:c.761C>T (p.Ser254Leu)

ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T

CaseAddInfo: Suspected Late Onset Pompe Disease, Nomenclature indicates Variants 2 and 3 are in cis

CaseOPOPD-5: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.97 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.503G>C (p.Arg168Pro)

CAID: CA401361673 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.503G%3EC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation and One Pseudodeficency Mutation

Case#: P 14, Male, 1.5 months old when started ERT (Died at 41.8 months old), German

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0002090

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Pneumonia)

CaseHPOFreeText: Pneumonia and deterioration were complications during ERT

Required ventilation

CaseNotHPOs: N/A

CaseNotHPOFreeText: Did not required tube feeding

CasePreviousTesting: CRIM Status and Antibody titer are unknown

Variant: NM_000152.5(GAA):c.1978C>T (p.Arg660Cys)

ClinVar:<br /> 558604

CAID: CA8815561

gnomAD: MAF=0.00005554 in East Asian

ParentalGenotype: Both the paternal and maternal allele carry the variant c.1978C>T (p.Arg660Cys)

PreviouslyPublished: N/A

Case#: P 5, Male, 0.9 months old when started ERT (76.9 months old at publication date), Ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639 , HP:0001252 , HP:0003701, HP:0006532

(Hypertrophic cardiomyopathy, Muscular hypotonia, Proximal muscle weakness, Recurrent pneumonia)

CaseHPOFreeText: Recurrent pneumonia was a complication during ERT.

AR III

Patient requires tube feeding and is ventilated

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CRIM status is unknown

Antibody titer is 1:12,000

Variant: NM_000152.5(GAA):c.2662G>T (p.Glu888Ter)

ClinVar: 578595

CAID: CA8815829

gnomAD: Highest population MAF= 0.0002719 (East asian)

ParentalGenotype: Both the paternal and maternal allele carry the c.2662G>T (p.Glu888Ter) Variant

PreviouslyPublished: N/A

Patient5: 12yo

CasePresentingHPOs: HP:0001638

HPOsFreeText: rhGAA dosage = 20 EOW, ventilator dependent

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 6mo at ERT start

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.3:c.2023_2025del

CAID: CA274244, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA274244

gnomAD: 2.105e-05, http://exac.broadinstitute.org/variant/17-78086806-CACA-C

Patient8: 2yo

CasePresentingHPOs: HP:0001638

HPOsFreeText: rhGAA dosage = 40 EOW, independent walker

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 16 days old at ERT start

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2:NM_000152.3:c.1197_1208del

CAID: CA658795246, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795246

gnomAD: n/a

Case#: Subject number 10, male, 70 years (report), 58 years (onset), 65 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walking stick occasionally)

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (tinnitus, hypothyroidism, scoliosis, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2655_2656delCG (p.Val886GlufsTer2)

Variant 2 ClinVarID: 597005

Variant 2 CAid: CA913191011

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18, male, 65 years (report), 40 years (onset), 62 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000939 (osteoporosis), HP:0001638 (cardiomyopathy)

CaseHPOFreeText: ambulatory, on BiPAP

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0009830, HP:0100647, HP:0010788 (tinnitus, hypothyroidism, scoliosis, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer)

CaseNotHPOFreeText: no tracheostomy, no infusion reaction

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1051delG

Variant 2 ClinVarID: 188841

Variant 2 CAid: CA274024

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 6, female, 57 years (report), 20s years (onset), 31 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650 (scoliosis)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walker)

CaseNotHPOs: HP:0000360, HP:0000365, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (tinnitus, hearing loss, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case16HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.1 umol/h/L, GAA activity at 33% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.722_723delTT (p.Phe241Cysfs*?)

CAID: CA658795235 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.722_723delTT

gnomAD: Not in gnomAD

CaseAddInfo:

Case12HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 4 nmol/punch/hr, GAA activity at 15% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.546+1G>T

CAID: CA401361913 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.546%2B1G%3ET

gnomAD: Not in gnomAD

CaseAddInfo:

Case#: Subject number 10, male, 46 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0002153 (hyperkalemia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.36 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.236_246delCCACACAGTGC (p.Pro79ArgfsTer13)

Variant 2 ClinVarID: 371302

Variant 2 CAid: CA16041880

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 8, female, 32 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.3 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13, female, 57 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

Variant 2 ClinVarID: 188484

Variant 2 CAid: CA198797

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case33: Female, 79 years report

HPOsFreeText: ERT not started, 6 Minute Walking Test at 312 meters, Forced Vital Capacity at 113%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.1560C>G (p.Asn520Lys)

CAID: CA401367200 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1560C%3EG

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case16: Female, 61 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 392 meters, Forced Vital Capacity at 52%

GenotypingMethod: GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.693-1G>C

CAID: CA401362948 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.693-1G%3EC

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease

Case#: Patient, female, 61 years old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0040213, HP:0010535, HP:0003326, HP:0002273, HP:0002877 (Hypopnea, Sleep Apnea, Myalgia, Tetraparesis, Nocturnal hypoventilation)

CaseHPOFreeText: Sleep Apnea-Hypopnea Syndrome (SAHS), predominantly proximal tetraparesis

CaseNotHPOs: N/A

CaseNotHPOFreeText: Serum measurements were normal, includind Creatine Phosphokinase levels (CPK)

CasePreviousTesting: GAA enzyme level 0.72 µkat/kg was significantly reduced in lymphocytes with a reference range of 4.8–13.3 µkat/kg protein. This test was done with maltase-glucoamylase inhibitor acarbose

All exons and flanking introns were bidirectionally sequenced after PCR amplification. "sequence-analysis of GAA transcripts"

Variant: c.1194+5G>A

ClinVar:

CAID:CA658795243

gnomAD:

ParentalGenotype:

PreviouslyPublished: N/A

Case20: Male, 8 years onset, 11 years diagnosis, 11 years report

CasePresentingHPOs: HP:0003236 (Increased serum CK)

HPOsFreeText: Asymptomatic hyperCKemia

CaseAddInfo: Late-Onset Pompe Disease

Case12: Female, Unknown years onset, Unknown years diagnosis, 50 years report

CasePresentingHPOs: HP:0003325, HP:0003327, HP:0003236, HP:0002747 (Limb-girdle muscle weakness, Axial muscle weakness, Increased serum CK, Respiratory muscle weakness)

CaseAddInfo: Late-Onset Pompe Disease

Case#: Patient 10, Gender N/A, Onset at 1-2 months. Death at 10 months, Southeast Asian

DiseaseAssertion:Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639. HP:0005165, HP:0002100

(Dyspnea, Shortened PR interval, Recurrent aspiration pneumonia)

CaseHPOFreeText: BVH, SDD

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting GAA enzyme activity is not available.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant: NM_000152.5(GAA):c.876C>G (p.Tyr292Ter)

ClinVar: 637958

CAID: CA500127534

gnomAD: N/A

ParentalGenotype: Both parents are carriers of the variant c.876C>G (p.Tyr292Ter)

PreviouslyPublished: N/A

Patient2: Female, northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

Variant2: NM_000152.3:c.859-2A>T

CAID: CA401363789, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401363789

gnomAD: n/a

Case12

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.2560C>T (p.Arg854*)

ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Variant2: NM_000152.4:c.1654delC (p.Leu552Serfs*26)

CAID: CA658795262 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1654delC

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease

Case65

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.1798C>T (p.Arg600Cys)

CAID: CA8815481 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1798C%3ET

gnomAD: South Asian 3.267e-5, Overall 4.025e-6 http://gnomad.broadinstitute.org/variant/17-78086420-C-T

Variant2: NM_000152.4:c.-32-13T>G

ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease

Patient9: Female, Northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.796C>T (p.Pro266Ser)

ClinVar: 556117, https://www.ncbi.nlm.nih.gov/clinvar/variation/556117/

gnomAD: n/a

Variant2: NM_000152.3:c.1602_1605delinsAGG

CAID: CA913184733, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184733

gnomAD: n/a

Patient21: Female, Northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1802C>T (p.Ser601Leu)

ClinVar: 194154, https://www.ncbi.nlm.nih.gov/clinvar/variation/194154/

gnomAD: n/a

Variant2: NM_000152.3:c.1844G>T

CAID: CA401369601, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401369601

gnomAD: n/a

Patient24: Female, Northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: c.1151 + 2T > G no ClinVar or CAID, intronic position inside exon

Variant2: NM_000152.3:c.1562A>T

CAID: CA401367205, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401367205

gnomAD: 0.000003980, http://gnomad.broadinstitute.org/variant/17-78084750-A-T

Patient16: Male

CasePresentingHPOs: HP:0004887, HP:0002194, HP:0001522

HPOsFreeText: ERT dosage = 29mg/kg/2w

CaseNotHPOs:

NotHPOsFreeText: No HCM reversal

CaseAddInfo: Symptom onset at 2days, diagnosis and ERT at 10mo, ERT lasted for 6mo, required ventilation at 11mo, died at 16mo

CasePMIDs: 14695532

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.3:c.1431del

CAID: CA502178465, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA502178465

gnomAD: n/a

Patient9: Male

CasePresentingHPOs: HP:0004887, HP:0002194, HP:0001522

HPOsFreeText: ERT dosage = 20 mg/kg/2 w, CRIM negative

CaseNotHPOs:

NotHPOsFreeText: no HCM reversal

CaseAddInfo: Symptom onset at 2mo, diagnosis at 4mo, ERT at 4.5mo, ERT lasted for 4mo, ventilation required at 7mo, died at 10mo

CasePMIDs: 22252923, 27629047

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.3:c.1657C>T

CAID: CA401368835, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.1657C%3ET

gnomAD: n/a

Case#: Patient 3, female, symptoms began at birth, diagnosed at 5 weeks

DiseaseAssertion: Pompe Disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639, HP:0003712 (hypertrophic cardiomyopathy, hypertrophy of calves)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: <1% normal GAA expression in fibroblast; after ERT treatment had 100% enzyme activity in cell lysates; unclear how patient was diagnosed

Variant 1: NM_000152.5:c.525delT

Variant 1 ClinVarID: 4033

Variant 1 CAid: CA220406

Variant 2: NM_000152.5:c.525delT

Variant 2 ClinVarID: 4033

Variant 2 CAid: CA220406

ParentalGenotype: Not provided

Case4: Female, 16 years diagnosis, 13 years onset

CasePresentingHPOs: HP:0009073, HP:0003198, HP:0003236, HP:0003327, HP:0008994 (Progressive proximal muscle weakness, Myopathy, Increased serum CK, Axial muscle weakness, Proximal muscle weakness in lower limbs)

HPOsFreeText: Electromyography showed myogenic damage, Vacuolar myopathy, Serum CK is 1652.0 U/L

Case#: Patient 3, Female, 2 months old at diagnosis, Caucasian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001252, HP:0001638

(Muscular hypotonia, Cardiomyopathy)

CaseHPOFreeText: floppy baby, no head or neck control

NG tube feeds started at age 1.4 months, currently the patient orally feeds.

Before ERT patient needed oxygen, currently the patient does not need respiratory support.

CaseNotHPOs:

CaseNotHPOFreeText:

Patient ambulates independently

No infusion associated reactions to ERT

CasePreviousTesting: No GAA measurement

Variant: NM_000152.5(GAA):c.236_246del (p.Pro79fs)

ClinVar: 371302

CAID: CA16041880

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

CasePD/VOUS-5: 1.7 years diagnosis

HPOsFreeText: GAA activity 9.16 (nmol · h−1 · mg−1), Mean percentage of normal 12.9%

GenotypingMethod: Newborn Screening Panels

Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant2: NM_000152.4:c.2065G>A (p.Glu689Lys)

ClinVar: 4030 https://www.ncbi.nlm.nih.gov/clinvar/variation/4030/

gnomAD: East Asian 0.2355, Overall 0.05524 http://gnomad.broadinstitute.org/variant/17-78087041-G-A

Variant3: NM_000152.4:c.1424C>T (p.Pro475Leu)

CAID: CA8815314 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3:c.1424C%3ET

gnomAD: South Asian 1.307e-4, Overall 2.009e-5 http://gnomad.broadinstitute.org/variant/17-78083841-C-T

CaseAddInfo: Patient has one pseudodeficency allele and one allele of uncertain significance, Nomenclature claims Variant 1 and 2 are in cis

Case3: Patient ID C, Male, 12 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Hematoma

CaseNotHPOs: HP:0000967, HP:0000979, HP:0000978, HP:0004406, HP:0000225, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, easy bruising, recurrent epistaxis, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemhorrage after dental, hemhorrage after trauma, ear bleeding

ProteinExpression: N/A

PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin

CasePreviousTesting: Exon PCR was used to amplify a;; coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.

Gene: ITGA2B

Variant: NM_000419.3:c.1233C>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399803781

gnomAD: N/A

PreviouslyPublished: PMID: 12424194

Case10: Patient ID J, Female, 5 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Related to Patient's I and K (See Table 1)

ParentalGenotype: N/A (Parents are consangenous)

CasePresentingHPOs: HP:0000978, HP:0004406, HP:0000225, HP:0002239

(Easy bruising, recurrent epistaxis, gingival bleeding, GI bleeding

CaseHPOFreeText: Hemorrhage after trauma, hematoma

CaseNotHPOs: HP:0000967, HP:0000979, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dental, ear bleeding

ProteinExpression: N/A

PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin

CasePreviousTesting: Exon PCR was used to amplify coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.

Gene: ITGA2B

Variant: NM_000419.3:c.1652G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

gnomAD: MAF in South Asian population is 0.00006536 http://gnomad.broadinstitute.org/variant/17-42457470-C-T

PreviouslyPublished: PMID: 19172520

Case15: Family L (patient found in the GT database as well) gender and age are not specified here

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225(Epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

PreviouslyPublished: Reference numbers 26,27 in this article

Case8: Patient Mila-1 (found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 25% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His)

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

PreviouslyPublished: Reference number 19 in this article

Case33: Patient GT3

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.777+1G>A and the second variant I am not sure how to write out

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623036

gnomAD: MAF in the Latino population is 0.0006774 https://gnomad.broadinstitute.org/variant/17-45363789-G-A

PreviouslyPublished: References 53-55

Case12: Patient CW (can be found in GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000979, HP:0000967, (Ecchymosis, Purpura/petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <1% of normal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.480C>G (p.Ser160_102del)

LegacyVariant: N/A

ClinVar: 2892 (Arg584Ter)

CAiD: CA115834 and CA399805892

gnomAD: MAF in the East Asian population is 0.0002176 for the Arg584Ter variant and MAF in the East Asian population is 0.00005507 for the other variant https://gnomad.broadinstitute.org/variant/17-42463013-G-C

PreviouslyPublished: Reference number 23 in this article

Case38: Patient IJ12

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000421, HP:0000225, HP:0002239, HP:0000979, HP:0000967, HP:0006298

(Epistaxis, gingival bleeding, GI bleeding, purpura/petechiae, prolonged bleeding after tooth extraction)

CaseNotHPOsFreeText: N/A

ProteinExpression: <2% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

PreviouslyPublished: References 8-12

Supplementary Table S1 & S2 Proband and Variant Information:

Case19: GT22, Male, 13, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000225

(Easy bruising, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.408+11C>A and NM_000419.3:c.1259T>C (p.Val420Ala)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940333 and CA399803733

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case17: GT20, Male, 28, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0005261

(Epistaxis, hemarthrosis)

CaseHPOFreeText: Occasional hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 10-20% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.2800G>T (p.Val934Phe)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290946484

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case64: GT67, Male, 61 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is now dead (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs:

(Gingival bleeding, epistaxis, bleeding after dental extraction )

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.1618C>T (p.Gln540Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA399802411

gnomAD: MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42457504-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case27: GT31, Female, 13, USA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000421

(Gingival bleeding and epistaxis)

CaseHPOFreeText: Life-threatening bleeding at onset of menses

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1771dup (p.Asp591Glyfs*47) and NM_000419.3:c.3061-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940334 and CA399787972

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case69: GT73, Female, 34 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000421, HP:0000225, HP:0000132

(Ecchymosis, epistaxis, gingival bleeding, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed nromal to reduced αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.889G>A (p.Gly297Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623074

gnomAD: MAF in the European (non-Finnish) population is 0.00002643 https://gnomad.broadinstitute.org/variant/17-45364547-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case1: GT1, Male, 9, French/African

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0011890, HP:0000421, HP:0000225

(Bruising susceptibility, prolonged bleeding following procedure, epistaxis, gingival bleeding)

CaseHPOFreeText: Tonsilar hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.1913+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032825

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967, HP:0030137

(Epistaxis, purpura, ecchymosis, petechiae, prolonged bleeding at circumcision)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.614+1G>T and NM_000212.2:c.683G>A (p.Arg228His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023344 and CA8623025

gnomAD: MAF in the African population is 0.00008012 http://gnomad.broadinstitute.org/variant/17-45363694-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case56: GT57, Female, 10, Argentinian/European

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000967

(Epistaxis, petechia)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.571T>G (p.Phe191Val) and NM_000419.3:c.961G>T (p.Phe191Alafs*32)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805699 and CA399804768

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967

(Epistaxis, purpura, ecchymosis, petechiae)

CaseHPOFreeText: Lots of bleeding at circumcision

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.614+1G>T and NM_000212.2:c.683G>A (p.Arg228His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023344 and CA8623025

gnomAD: MAF in the African population is 0.00008012 http://gnomad.broadinstitute.org/variant/17-45363694-G-A

Case13: Patient NA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

Variant: There is a typo in this article, the article states Glu500Ter however it is Gln. NM_000419.3:c.1591C>T (p.Gln531Ter)

LegacyVariant: (p.Gln500Ter)

ClinVar: N/A

CAiD: CA399802478

gnomAD: N/A

Case12: 2 Females, age not specified "Two sisters" is what the Table mentions

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002239

(Gastrointestinal bleeding)

CaseHPOFreeText: Life threatening bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting:

Gene: ITGB3 and ITGA2B

Variant: NM_000212.2:c.392G>C (p.Arg131Pro in ITGB3) and NM_000212.2:c.777+1G>A in ITGB3 and NM_000419.3:c.2264G>A (p.Arg755Gln) in ITGA2B

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

gnomAD: MAF in the African population 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C , MAF in Latino population 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A and MAF in Latino population 0.0001903 (p.Arg775Gln)

Case24: Male, age not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding (See Table 1 for Clinical and Biological Data-- minimal information)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.

Gene: ITGB3

Variant: NM_000212.2:c.1619G>A (p.Gly540Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400030071

gnomAD: N/A

Case10 : Female, age not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asp314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case20b: GT20b, Female, 23 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family information available in Table1 (sister of proband GT20a)

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0002239, HP:0000132

(Bruising, purpura, ecchymosis, gastrointestinal bleeding, menorrhagia)

CaseHPOFreeText: Post traumatic bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

gnomAD: MAF in Latino population: 0.00003983 https://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Tables 1 and 2 combined information:

Case35: GT35, Male, 1 year old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364

(Bruising, purpura, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.625-1G>A (c.625-1G>A) and NM_000419.3:c.659A>G (p.Tyr220Cys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805552 (c.625-1G>A) and CA399805484 (p.Tyr220Cys)

gnomAD: MAF for (p.Tyr220Cys) in the South Asian population 0.00003266 https://gnomad.broadinstitute.org/variant/17-42462543-T-C

Supplementary Tables 1 and 2 combined information:

Case26: GT26, Male, 13 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364

(Bruising, purpura, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (Gln778Pro) and NM_000419.3:c.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro)

CAiD: CA290947544 (p.Gln778Pro) and CA8602626 (p.Gln891Ter)

gnomAD: MAF in East Asian population: 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Tables 1 and 2 combined information:

Case12: GT12, Male, 10 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family history available per Table 1; however, no further information given

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case29: GT29, Female, 16 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000132, HP:0000978, HP:0000979, HP:0031364, HP:0000225

(Menorrhagia, bruising, purpura, ecchymosis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

gnomAD: MAF in the East Asian population: 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Tables 1 and 2 combined information:

Case22: GT22, Female, 16 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000132 (Menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

gnomAD: MAF in the East Asian population: 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Tables 1 and 2 combined information:

Case4: GT4, Female, 22 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225, HP:0000132

(Bruising, purpura, ecchymosis, epistaxis, gingival bleeding, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGA2B

Variant: NM_000419.3:c.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602626

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case41: GT41, Male, 5 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGB3

Variant: NM_000212.2:c.1736G>A (p.Trp579Ter) and NM_000212.2:c.1784_1802delinsGTCACA

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032429 (p.Trp579Ter) and CA915940255 (c.1784_1802delinsGTCACA)

gnomAD: N/A

Case#: patient 2

DiseaseAssertion: Glanzmann thrombasthenia

**FamilyInfo: **

ParentalGenotype: If noted by authors, annotate with the carrier status of each parent in regards to the variant(s) identified in the proband.

CasePresentingHPOs:

PlateletAggregation: absent platelet integrin αIIbβ3. Monolayer of spread platelets essentially devoid of fibrinogen binding but with high CD62P expression and phosphatidylserine exposure (Figure S1). Figure 5.

CaseHPOFreeText:

CaseNotHPOs:

**CaseNotHPOFreeText: **

ProteinExpression:

CasePreviousTesting:

**PreviouslyPublished: **

Gene: ITGA2B

**HGVS: **

**ClinVar: **

CAID:

**gnomAD: **

Gene: ITGA2B

**HGVS: ** NM_000419.5:c.2051T>G

**ClinVar: ** 1330350

CAID: CA399799849

**gnomAD: **

Supplemental Table S1:

Cases26-33: Males and Females from France, Spain and Italy and ages are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mild to severe bleeding for probands

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 8-20% αIIbβ3 expression

PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)

CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed

Gene: ITGA2B

Variant: NM_000419.3:c.2113T>C (p.Cys705Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602816

gnomAD: MAF in the European non finnish population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G

PreviouslyPublished: PMID: 9920835, 12083483, 12424194, 25728920, 20020534

Supplemental Table S1:

Case3: Male, USA, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe life threatening bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: >5% αIIbβ3 expression

PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)

CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed

Gene: ITGA2B

Variant: NM_000419.3:c.1553T>A (p.Ile518Asn) and NM_000419.3:c.1946+3G>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603038 and CA626121071

gnomAD: MAF in the European (non-Finnish) population is 0.000008790 https://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A

PreviouslyPublished: PMID: 25728920

Supplemental Table S1:

Case5: Male, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding from multiple sites

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 8% αIIbβ3 expression

PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)

CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed

Gene: ITGA2B

Variant: NM_000419.3:c.1651C>T (p.Arg551Trp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

gnomAD: MAF in the East Asian population is 0.00005045 https://gnomad.broadinstitute.org/variant/17-42457471-G-A

PreviouslyPublished: PMID: 16879215

Case43: (GT-53) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Case35: (GT-45) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT45-GT48 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1879-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Case24: (GT-29) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT30 is related to GT29

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Moderate (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1651C>T (p.Arg551Trp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

gnomAD: MAF in the East Asian population is 0.00005045 http://gnomad.broadinstitute.org/variant/17-42457471-G-A

Case4: (GT-04) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-04 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Mild (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1210+5G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case6: (GT-07) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-07 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Mild (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1210+5G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case2: (GT-02) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-02 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: N/A for proband 2 (See Supplemental Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)