ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.175G>C (p.Gly59Arg) (rs1555937077)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516335 SCV000613478 likely pathogenic not provided 2018-12-27 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/199642 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Moderate co-segregation with disease in multiple families, but using affected individuals only.
Invitae RCV000654839 SCV000776741 uncertain significance Charcot-Marie-Tooth Neuropathy X 2018-09-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 59 of the GJB1 protein (p.Gly59Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie Tooth disease, type X (PMID: 10894999). 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: "Probably Damaging"; Align-GVGD: "Class C15"). A different missense substitution at this codon (p.Gly59Cys) has been reported in an individual affected with Charcot-Marie Tooth disease, type X  (PMID: 10093067). This suggests that the glycine residue may be critical for GJB1 protein function 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 RCV000789852 SCV000929237 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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