Submissions for variant NM_004183.4(BEST1):c.851A>G (p.Tyr284Cys)

dbSNP: rs727503824

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723944	SCV000202249	uncertain significance	not provided	2014-04-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000723944	SCV000616654	likely pathogenic	not provided	2023-09-13	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35754583, 33090715, 21109774, 35973442, 32207364)
Invitae	RCV000723944	SCV001206721	pathogenic	not provided	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 284 of the BEST1 protein (p.Tyr284Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant BEST1-related conditions (PMID: 21109774, 32207364; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 166746). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BEST1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262506	SCV001440413	likely pathogenic	Vitelliform macular dystrophy 2	2019-01-01	criteria provided, single submitter	clinical testing
Department of Genetics, Fundacion Jimenez Diaz University Hospital	RCV001270355	SCV001450582	likely pathogenic	Stargardt disease		criteria provided, single submitter	clinical testing	Variant not found in gnomAD. Same amino acid change previously reported pathogenic (ClinVar: VCV000813024.1, predicted deleterious by in-silico pathogenicity predictors. (ACMG: PS2 Strong; PM2 Moderate; PP3 Supporting)