ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.282C>A (p.His94Gln)

dbSNP: rs756000896
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236380 SCV000292796 likely pathogenic not provided 2023-10-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 9361298, 11325342, 16311287, 21280457, 28286897, 18648547)
Labcorp Genetics (formerly Invitae), Labcorp RCV001854850 SCV002146918 pathogenic Charcot-Marie-Tooth Neuropathy X 2021-08-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His94 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11325342, 28768847; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GJB1 function (PMID: 11325342). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 245724). This missense change has been observed in individuals with GJB1-related conditions (PMID: 11325342, 11571214, 14680548, 18379723, 28286897). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 94 of the GJB1 protein (p.His94Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine.
Inherited Neuropathy Consortium RCV000789853 SCV000929238 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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