Hypothesis

Patient P2 A 42-year-old woman was referred to the Eye Clinic due to a lesion in OS. OD was normal. BCVA was 20/25, and a peripheral RCH with a macular pseudohole was observed at the fundoscopic examination (Figure 3). The tumor was treated using laser photocoagulation and required several treatment sessions. One week after the first laser session, the pseudohole progressed to a lamellar macular hole (LMH) and after some months, to a FTMH. BCVA worsened to 20/63 in 2012, and pars plana vitrectomy was successfully performed: The macular epiretinal membrane and internal limiting membrane were peeled. During follow-up, a retinal tear was detected (in 2014), and it was treated using a barrage laser. The last follow-up visit (in September 2019) revealed a good macular profile and RCH regression; BCVA in OS was 20/25. During the follow-up, OS did not develop lesions.

PatientID: 2

KindredID: 2

Case: F, 52Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: A family pedigree is provided. Both the mother and daughter of patient 2 were found to have the same mutation. Neither the 61-year-old mother, nor the 6-year-old daughter had RCHs. The mother had other tumours, which were not specified.

CasePresentingHPOs: HP:0001737; HP:0031152 (Retinal capillary hemangioma; full-thickness macular hole)

CaseHPOFreeText: The patient underwent a retinal examination at 42Y0M due to a lesion in her left eye. This eyes had 20/25 vision snd a peripheral retinal capillary hemangioma (RCH) was detected in this left eye and laser was performed. A week later it turned into a lamellar macular hole and she underwent a vitrectomy, her vision also got worse. In her follow up appointment in 2014, a retinal tear was detected and treated with laser. In 2019, the left eye did not develop any lesions (table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: Patient did not seem to have have any other tumours.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P192L (c.575C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 526677, https://www.ncbi.nlm.nih.gov/clinvar/variation/526677/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P192L (c.575C>T)

MultipleGeneVariants: N/Afa

InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transition FamilyPedigree DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:42 CivicName:P192L(c.575C>T) ClinVarID:Yes ClinVarID:526677 cDNAPosition:575 ProteinPosition:192 AminoAcidChange:PROtoLEU DiseaseEntity:VHL DiseaseEntity:full-thicknessmacularhole Familial AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:7010 inferred_gene_source:ClinVar VHL Hypothesis Annotation

P3F2F12661nyOU20/250nn20/25nnn

PatientID: 3

KindredID: 2

Case: F, 71Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: A family pedigree is provided. Patient’s daughter and granddaughter have the same mutation. Patient’s daughter had a retinal capillary hemangioma and lamellar macular hole in the left eye. The granddaughter did not seem to be affected.

CasePresentingHPOs: N/A

CaseHPOFreeText: The patient has tumours, but which she has were not specified (table 1).

CaseNotHPOs: HP:0001737 (Retinal capillary hemangioma)

CaseNotHPOFreeText: Patient did not have retinal capillary hemangiomas.