ClinVar Miner

Submissions for variant NM_004183.4(BEST1):c.934G>A (p.Asp312Asn)

gnomAD frequency: 0.00001  dbSNP: rs281865277
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000086205 SCV000322402 pathogenic not provided 2021-04-20 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; reduces chloride ion channel current and appears to inhibit wild-type function suggesting a possible dominant negative effect (Yu K et al., 2007; Johnson AA et al., 2014); 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: 19029375, 23290749, 24560797, 21330666, 19372599, 19375515, 27071392, 10854112, 28831140, 32239196, 18179881, 17898294, 22162627, 29555955)
Invitae RCV000086205 SCV001203933 pathogenic not provided 2023-09-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BEST1 function (PMID: 17898294, 21330666). 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. ClinVar contains an entry for this variant (Variation ID: 99786). This missense change has been observed in individuals with autosomal recessive bestrophinopathy (PMID: 18179881, 22162627, 23290749). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with clinical features of autosomal dominant Best vitelliform macular dystrophy (PMID: 10854112, 29555955, 32239196); however, the role of the variant in this condition is currently unclear. This variant is present in population databases (rs281865277, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 312 of the BEST1 protein (p.Asp312Asn).
Retina International RCV000086205 SCV000118349 not provided not provided no assertion provided not provided

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