atientID: II.1

KindredID: F6

Case: M, 0Y6M, Ethnicity Unknown

DiseaseAssertion: Splenomegaly

FamilyInfo: N/A

CasePresentingHPOs: HP:0001744 (Splenomegaly)

CaseHPOFreeText: Diagnosed with splenomegaly at age 6 months (DOB: 2014).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: c.340+574A>T

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 1040488, https://www.ncbi.nlm.nih.gov/clinvar/variation/1040488/

CAID: N/A

gnomAD: N/A

VariantEvidence: Variants are heterozygous.

MutationType: missense_variant;transversion; splice_site_variant

CivicName: Q164H (c.492G>T) and c.340+574A>T

MultipleGeneVariants: Germline, VHL, c.492G>T (p.Gln164His)

PatientID: None (Father)

KindredID: F6

Case: M, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164H (c.492G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 456566, https://www.ncbi.nlm.nih.gov/clinvar/variation/456566/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Q164H (c.492G>T)

MultipleGeneVariants: N/A

PatientID: 10

KindredID: 10

Case: 39Y0M, Sex and Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Recorded as a familial tumor; one other family info present (Patient ID: 9) who is a 47 year old patient with an abdominal paraganglioma

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Unilateral pheochromocytoma reported with an age at diagnosis of 39 years of age.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB/SDHC/SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164H (c.492G>C)

CaseProblemVariantFreeText: Paper stated this as c.491G>C; p.Q164H. cDNA position of 492 is most likely correct and matches up. Error by authors to say c.491.

LegacyVariant: N/A

ClinVarID: 618485 https://www.ncbi.nlm.nih.gov/clinvar/variation/618485/

CAID: N/A

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191499-G-C

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: Q164H (c.492G>C)

MultipleGeneVariants: N/A

PatientID: None (Proband)

KindredID: 24

Case: F, 14Y0M, EthnicityUnknown

DiseaseAssertion: VHL

FamilyInfo: 2/3 genetically tested individuals from a family with no family history of VHL disease were found to harbor the c.492G>T mutation causing a Gln164His missense variant (noted in the paper as c.705G>T due to Latif reference transcript being used). The proband presented with retinal capillary hemangioma and the other had unremarkable ophthalmoscopic findings (27Y, brother). The proband’s sister was negative for the variant.

CasePresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

CaseHPOFreeText: Patient had a clinical diagnosis of VHL disease. Presented with vision loss due to a single juxtapapillary angioma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Paper states that further screening did not find any other VHL lesion.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164H (c.492G>T)

LegacyVariant: c.705G>T

CaseProblemVariantFreeText: N/A

ClinVarID: 456566, https://www.ncbi.nlm.nih.gov/clinvar/variation/456566/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Q164H (c.492G>T)

MultipleGeneVariants: N/A

PatientID: 5

KindredID: 1

Case: Sex Unknown, 15Y10M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: None.

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: At first presentation (age 14Y3M) the patient had a visual acuity of 20/200. The angioma showed an exophytic growth pattern and was located in the inferior disc margin.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Medical screening for other VHL lesions comprised magnetic resonance imaging (MRI) of the brain and spinal cord (gadolinium-enhanced), urine catecholamines, and abdominal sonography or computed tomography (CT). No VHL lesions present other than the retinal angioma reported.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164H (c.492G>T)

LegacyVariant: p.Q164H (c.705G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 456566 https://www.ncbi.nlm.nih.gov/clinvar/variation/456566/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: Q164H (c.492G>T)

MultipleGeneVariants: N/A