Supplementary Data: S2 Table

Case 95: Spanish, 1yo, Female

DiseaseAssertion: Hypertrophic Cardiomyopathy

CasePreviousTesting: Full Testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data table S1

CaseGenotypingMethod: genomic DNA obtained from blood or saliva, Next-gen sequencing panels of 55 or 78 genes

Variant: NM_000257.3(MYH7):c.2608C>T (p.Arg870Cys)

ClinVar: 161326, https://www.ncbi.nlm.nih.gov/clinvar/variation/161326/

gnomAD: 0.00002386, https://gnomad.broadinstitute.org/variant/14-23894049-G-A

MultipleGeneVariants:

(1) TTN Variant:

Variant: NM_133378.4:c.8920A>G

CAID: CA61002480, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_133378.4%3Ac.8920A%3EG

gnomAD: n/a

Supplementary Data: S2 Table

Case 116: Spanish, 66yo, Female

DiseaseAssertion: Hypertrophic Cardiomyopathy

CasePreviousTesting: Full Testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data table S1

CaseGenotypingMethod: genomic DNA obtained from blood or saliva, Next-gen sequencing panels of 55 or 78 genes

Variant: NM_000257.3(MYH7):c.2167C>G (p.Arg723Gly)

ClinVar: 42885, https://www.ncbi.nlm.nih.gov/clinvar/variation/42885/

gnomAD: n/a

MultipleGeneVariants

(1) TTN Variant:

Variant: NM_133378.4:c.31738G>A

CAID: CA349484668, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_133378.4%3Ac.31738G%3EA

gnomAD: n/a

(2) MYBPC3 Variant:

Variant: NM_000256.3(MYBPC3):c.3676C>T (p.Arg1226Cys)

ClinVar: 42731, https://www.ncbi.nlm.nih.gov/clinvar/variation/42731/

gnomAD: 0.00004815, https://gnomad.broadinstitute.org/variant/11-47353761-G-A

Supplementary Data: S2 Table

Case 103: Spanish, 24yo, Male

DiseaseAssertion: Hypertrophic Cardiomyopathy

CasePreviousTesting: Full Testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data table S1

CaseGenotypingMethod: genomic DNA obtained from blood or saliva, Next-gen sequencing panels of 55 or 78 genes

Variant: NM_000257.3(MYH7):c.2389G>A (p.Ala797Thr)

ClinVar: 42901, https://www.ncbi.nlm.nih.gov/clinvar/variation/42901/

gnomAD: 0.00002386, https://gnomad.broadinstitute.org/variant/14-23894525-C-T

MultipleGeneVariants:

(1) TTN Variants:

Variant1: NM_001256850.1(TTN):c.28363G>A (p.Val9455Met)

ClinVar: 202551, https://www.ncbi.nlm.nih.gov/clinvar/variation/202551/

gnomAD: 0.00005702, https://gnomad.broadinstitute.org/variant/2-179571287-C-T

Variant2: NM_133378.4:c.19943T>G

CAID: CA2000580, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_133378.4%3Ac.19943T%3EG

gnomAD: 0.00001635, https://gnomad.broadinstitute.org/variant/2-179584544-A-C

Variant3: NM_133378.4(TTN):c.77273G>A (p.Arg25758Gln)

ClinVar: 47442, https://www.ncbi.nlm.nih.gov/clinvar/variation/47442/

gnomAD: 0.0002431, https://gnomad.broadinstitute.org/variant/2-179425882-C-T

Supplementary Data Table S3

Case: 353

DiseaseEntity: HCM

HPOsFreeText: left ventricular hypertrophy (LVH) ≥15 mm

InheritancePattern: n/a

CasePreviousTesting: MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1 (59 genes total tested)

CaseGenotypingMethod: NGS of 59 genes (Supplemental Table S1), pathogenic and likely pathogenic variants confirmed via Sanger Sequencing

Variant: NM_000257.4(MYH7):c.3158G>A (p.Arg1053Gln)

ClinVar: 155814 https://www.ncbi.nlm.nih.gov/clinvar/variation/155814/

gnomAD: 0.0006368, https://gnomad.broadinstitute.org/variant/14-23891476-C-T

MultipleGeneVariants:

(1) EYA4 Variant

Variant: NM_004100.5(EYA4):c.979G>A (p.Asp327Asn)

ClinVar: 191664 https://www.ncbi.nlm.nih.gov/clinvar/variation/191664/

gnomAD: 0.004341, https://gnomad.broadinstitute.org/variant/6-133802609-G-A

(2) TTN Variant

Variant: NM_133378.4:c.21031G>T (p.Glu7011Ter)

CAID: CA349496727 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_133378.4%3Ac.21031G%3ET

gnomAD: Not in gnomAD