Submissions for variant NM_004183.4(BEST1):c.728C>T (p.Ala243Val)

dbSNP: rs28940570

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000086167	SCV000704550	pathogenic	not provided	2017-02-04	criteria provided, single submitter	clinical testing
Invitae	RCV000086167	SCV001212418	pathogenic	not provided	2024-01-23	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 243 of the BEST1 protein (p.Ala243Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant macular dystrophy (PMID: 10854112, 28225368, 28559085). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2737). 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%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BEST1 function (PMID: 17065513, 24560797). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001075633	SCV001241260	pathogenic	Retinal dystrophy	2019-02-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000086167	SCV001245802	pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	BEST1: PP1:Strong, PM2, PM5, PS4:Moderate, PS3:Supporting
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000086167	SCV001446682	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV000002858	SCV001548129	likely pathogenic	Vitelliform macular dystrophy 2	2021-01-30	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000002858	SCV002581427	likely pathogenic	Vitelliform macular dystrophy 2	2022-03-03	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV003326112	SCV004032306	pathogenic	Autosomal dominant vitreoretinochoroidopathy	2023-08-21	criteria provided, single submitter	clinical testing	Criteria applied: PM5_STR,PS3_MOD,PS4_MOD,PM1,PM2_SUP,PP3
Institute of Human Genetics, University of Leipzig Medical Center	RCV003448243	SCV004175991	pathogenic	Vitelliform macular dystrophy 1	2023-11-29	criteria provided, single submitter	clinical testing	Criteria applied: PS4,PM5_STR,PS3_MOD,PM1,PM2_SUP
OMIM	RCV000002858	SCV000023016	pathogenic	Vitelliform macular dystrophy 2	2000-04-01	no assertion criteria provided	literature only
Retina International	RCV000086167	SCV000118311	not provided	not provided		no assertion provided	not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000002858	SCV000926520	likely pathogenic	Vitelliform macular dystrophy 2	2018-04-01	no assertion criteria provided	research