ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.8G>C (p.Trp3Ser)

dbSNP: rs1555936989
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000654850 SCV000776752 uncertain significance Charcot-Marie-Tooth Neuropathy X 2021-07-14 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with serine at codon 3 of the GJB1 protein (p.Trp3Ser). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and serine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 8737658). 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 C0"). Experimental studies have shown that this missense change affects GJB1 protein function (PMID: 10646523). This variant disrupts the p.Trp3 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 8737658, 21922480), which suggests that this may be a clinically significant amino acid residue. 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.
Molecular Genetics Laboratory, London Health Sciences Centre RCV000789228 SCV001336649 pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789228 SCV000928580 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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