PatientID: 14

KindredID: 8

Case: M, 35Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: No details regarding family information is provided.

CasePresentingHPOs: N/A

CaseHPOFreeText: Patient has VHL disease characterized by tumours, but specific types of tumours were not indicated

CaseNotHPOs: HP:0010797; HP:0009711 (hemangioblastoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: Patient did not have CNS hemangioblastoma or Retinal capillary hemangiomas.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E52* (c.154G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182982, https://www.ncbi.nlm.nih.gov/clinvar/variation/182982/

CAID: N/A

gnomAD: 0.00001795, https://gnomad.broadinstitute.org/variant/3-10183685-G-T

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E52* (c.154G>T)

MultipleGeneVariants: N/A

GroupID: 36

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: This individual patient was the only one discussed with this mutation. They had retinal hemangiomas; Other VHL manifestations were discussed but not per- variant.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes - Supplementary Table S1

Variant: p.P154L (c.461C>T)

LegacyVariant: N/A

GroupProblemVariantFreeText: N/A

ClinVarID: 649525 https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: F42

Case: Sex unknown, 13Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: familial antecedents of clear cell carcinoma and renal cysts were found

CasePresentingHPOs: HP:0009711; HP:0006880; HP:0001737 (retinal capillary hemangioma, cerebellar hemangioblastoma, pancreatic cysts)

CaseHPOFreeText: Age of onset is 13Y0M.

CaseNotHPOs: HP:0002666; HP:0006770; HP:0000107 (pheochromocytoma, clear cell renal cell carcinoma, renal cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154P (c.462A>G)

LegacyVariant: g.8665A>G (splice-site)

CaseProblemVariantFreeText: Patient was reported with the g. (genomic) coding positions. The g.8665A>G variant worked out to correspond with p.P154P (c.462A>G). This also happens to be a synonymous variant, not a splice variant like the paper calls it.

ClinVarID: 411977 https://www.ncbi.nlm.nih.gov/clinvar/variation/

CAID: N/A

gnomAD: 0.000003976 https://gnomad.broadinstitute.org/variant/3-10188319-A-G

VariantEvidence: N/A

MutationType: synonymous_variant

CivicName: P154= (c.462A>G)

MultipleGeneVariants: N/A

PatientID: BCB-D-59

KindredID: 1

Case: Sex Unknown, Age Unknown, Saudi

DiseaseAssertion: Breast carcinoma

FamilyInfo: No family information reported.

CasePresentingHPOs: HP:0003002 (breast carcinoma)

CaseHPOFreeText: Patient has breast carcinoma. No other information is provided.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Ion AmpliSeq™ BRCA1 and BRCA2 Panel.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E52* (c.154G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182982, https://www.ncbi.nlm.nih.gov/clinvar/variation/182982/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E52* (c.154G>T)

MultipleGeneVariants: Germline, TP53, c.241C>T (p.R81X); Germline, MLH1, c.208-1G>C (p.E52X)

PatientID: 89

KindredID: 89

Case: F, 39Y0M, Chinese (East Asian)

DiseaseAssertion: Paraganglioma

FamilyInfo: No family history.

CasePresentingHPOs: Paraganglioma (HP:0002668)

CaseHPOFreeText: retroperitoneal paraganglioma 6.8cm in size; metastatic. Age of diagnosis at 39Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154S (c.460C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 486714 https://www.ncbi.nlm.nih.gov/clinvar/variation/486714

CAID: N/A

gnomAD: N/A

VariantEvidence: Described as a pathogenic variant, according to the ACMG guidelines at the time of publication.

MutationType: missense_variant;transition

CivicName: P154S (c.460C>T)

MultipleGeneVariants: N/A

GroupID: 2

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: N/A

CaseHPOFreeText: Manifestations are possibly but not clearly reported

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E52K (c.154G>A)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 161402 https://www.ncbi.nlm.nih.gov/clinvar/variation/161402/

CAID: N/A

gnomAD: 0.00008525 https://gnomad.broadinstitute.org/variant/3-10183685-G-A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: E52K (c.154G>A)

MultipleGeneVariants: N/A

GroupID: 35

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: other manifestations are not clearly stated.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154P (c.462A>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA16621934 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.462A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: synonymous_variant

CivicName: P154= (c.462A>C)

MultipleGeneVariants: N/A

PatientID: II-5

KindredID: B

Case: M, 25Y0M, Ethnicity Unknown

DiseaseAssertion: unknown

FamilyInfo: Two members were confirmed with this germline mutation (II-4 and II-5) c.462A>C and C to T transition at nucleotide 9. Blood from the father (I-1) and one sister (II-2) revealed no mutation. The paper states that the mother (I-2), and two siblings (II-3 and II-6) had died of VHL disease (no further information given though).

CasePresentingHPOs: N/A

CaseHPOFreeText: had clinical VHL manifestations which were not described

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154P (c.462A>C)

LegacyVariant: p.Leu to Leu (c.675A>C)

CaseProblemVariantFreeText: The tumor and blood samples from this patient also showed a C to T transition at nucleotide 9, but this nucleotide change did not alter the amino acid residue encoded and thus appeared to be a polymorphism

ClinVarID: N/A

CAID: CA16621934 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.462A%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: synonymous_variant

CivicName: P154= (c.462A>C)

MultipleGeneVariants: N/A