ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.248T>G (p.Leu83Arg) (rs1602349004)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001318400 SCV001509099 uncertain significance Charcot-Marie-Tooth Neuropathy X 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 83 of the GJB1 protein (p.Leu83Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (CMT) (PMID: 23011429, Invitae). ClinVar contains an entry for this variant (Variation ID: 637242). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GJB1 protein function (PMID: 30737405). This variant disrupts the p.Leu83 amino acid residue in GJB1. Other variant(s) that disrupt this residue have been observed in individuals with GJB1-related conditions (PMID: 10093067), 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.
Inherited Neuropathy Consortium RCV000789313 SCV000928666 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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