Case#: Patient 37 yo, F, Eastern Asian, onset at 8yo (early onset), Heterozygous, AR inheritance patterns

DiseaseAssertion:Retinitis Pigmentosa (RP)

FamilyInfo: Two brothers with RP and father with poor vision at 30 yo but no formal diagnosis

CasePresentingHPOs: HP:0003581, HP:0007737, HP:0000510, HP:000133

CaseHPOFreeText: N/A

CaseNotHPOs: HP: 0000007, HP:0007663, HP:0000505, HP:0000662

CaseNotHPOFreeText: N/A

Genotyping Method: N/A

PreviouslyPublished: Panel of genes; RP1L1, RP-GRIP1, ABCA4, and GRM6

Variant: c.5501T>C p.(Met1019Ille)

ClinVar: 1481089

SupplementalData: see tables 1 and 2 for genetic variant panel

When expressed in transfected HEK293T cells and quantified by Western blotting, this variant was in the range of 40%-52%. This variant has a basal ATPase activity of 63% ± 5% compared to WT (100%) and was categorized as class 2 (partial reduction in expression and basal ATPase activity that was modestly stimulated by N-Ret-PE) with a moderate/severe predicted severity.

ATPase function of G863A mutant protein was reduced ∼3-fold as compared with NBD1wt, indicating ∼70% of inhibition of the ATPase activity (Fig. 3). TheVmax (ATPase) for G863A mutant was 128 pmol/min/mg and that of the wild-type NBD1 was 584 pmol/min/mg (Table II).

GroupID/ KindredID: 28

PatientID: II

Case: 24Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 27Y) was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs, another (40Y) diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs, and a final relative (62Y), diagnosed with a single HAB.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed with a single cerebellar HAB at 24Y

GroupNotHPOs: HP:0009713; HP:0009711; HP:0005584 (spinal hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: F28

Case: Sex unknown, 23Y0M, Spanish

DiseaseAssertion: assumed VHL

FamilyInfo: familial antecedents found; unknown of any additional features of index case relatives

CasePresentingHPOs: HP:0000107; HP:0009711; HP:0006880; HP:0006770; HP:0002666 (renal cysts, retinal capillary hemangioma, cerebellar hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma)

CaseHPOFreeText: unilateral pheo, bilateral ccRCC and multiple lesions were found with the patient’s renal cysts. Age of onset is 23Y0M.

CaseNotHPOs: HP:0001737 (pancreatic cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: rearrangement (unspecified)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Southern blot positive

MutationType: rearrangement_region

CivicName: Rearrangement

MultipleGeneVariants: N/A

PMID:34884460

GeneName:GRIN1

ClinVarID:209159

ClinVarID:397504

ClinVarID:1076783

ClinVarID:658023

ClinVarID:430264

ClinVarID:487503

ClinVarID:691274