ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.14G>T (p.Gly5Val) (rs1064793139)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480735 SCV000565041 uncertain significance not provided 2021-05-18 criteria provided, single submitter clinical testing Reported in an individual with a mitochondrial respiratory chain disease; however, segregation analysis and additional clinical information were not provided (DeBrosse et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27812541)
Invitae RCV000697574 SCV000826194 uncertain significance Charcot-Marie-Tooth Neuropathy X 2018-11-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 5 of the GJB1 protein (p.Gly5Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with mitochondrial respiratory chain disease (PMID: 27812541). ClinVar contains an entry for this variant (Variation ID: 418234). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Gly5Ser) has been reported in an individual affected with Charcot-Marie-Tooth disease, type X (PMID: 21291455). 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.
Inherited Neuropathy Consortium RCV001027491 SCV001190066 likely pathogenic Charcot-Marie-Tooth disease no assertion criteria provided research
Natera, Inc. RCV001027491 SCV001462641 uncertain significance Charcot-Marie-Tooth disease 2020-09-16 no assertion criteria provided clinical testing

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