ClinVar Miner

Submissions for variant NM_001079866.2(BCS1L):c.385G>A (p.Gly129Arg)

dbSNP: rs1057521059
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000432529 SCV000520844 pathogenic not provided 2021-02-25 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on oxidative phosphorylation (Tuppen et al., 2010).; Not observed in large population cohorts (Lek et al., 2016); 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: 30582773, 22991165, 20472482)
Baylor Genetics RCV001329213 SCV001520588 likely pathogenic Leigh syndrome 2019-09-30 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. Phenotype is variable including muscle weakness, lactic acidosis, variable neuro-psychiatric manifestations and cortical visual dysfunction [PMID 20472482, 22991165]
Invitae RCV000432529 SCV002228280 pathogenic not provided 2021-10-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 129 of the BCS1L protein (p.Gly129Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of mitochondrial complex III deficiency (PMID: 20472482, 22991165). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 381524). 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 BCS1L protein function. Experimental studies have shown that this missense change affects BCS1L function (PMID: 20472482). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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