ClinVar Miner

Submissions for variant NM_004183.4(BEST1):c.851A>G (p.Tyr284Cys) (rs727503824)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723944 SCV000202249 uncertain significance not provided 2014-04-16 criteria provided, single submitter clinical testing
GeneDx RCV000723944 SCV000616654 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing The Y284C variant in the BEST1 gene has been reported previously in an individual with Best macular dystrophy (Cohn et al., 2011). This variant has also been observed in other individuals undergoing BEST1 testing at GeneDx. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y284C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret Y284C as a variant of uncertain significance.
Invitae RCV000723944 SCV001206721 uncertain significance not provided 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 284 of the BEST1 protein (p.Tyr284Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant vitelliform macular dystrophy (PMID: 21109774). ClinVar contains an entry for this variant (Variation ID: 166746). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center RCV001262506 SCV001440413 likely pathogenic Vitelliform macular dystrophy type 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)

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