Submissions for variant NM_004183.4(BEST1):c.244C>G (p.Leu82Val)

dbSNP: rs281865530

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000086105	SCV003440389	pathogenic	not provided	2023-03-08	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 99696). This missense change has been observed in individuals with autosomal dominant Best macular dystrophy (PMID: 10394929, 19357557, 20375334). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 82 of the BEST1 protein (p.Leu82Val). 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. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects BEST1 function (PMID: 21878505).
Retina International	RCV000086105	SCV000118249	not provided	not provided		no assertion provided	not provided
Clinical Genetics, Academic Medical Center	RCV000086105	SCV001924327	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000086105	SCV001954156	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000086105	SCV001970680	pathogenic	not provided		no assertion criteria provided	clinical testing