ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.148T>C (p.Ser50Pro) (rs913934445)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493545 SCV000582848 likely pathogenic not provided 2017-05-22 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the GJB1 gene. The S50P variant has been previously reported in two families with a clinical diagnosis of axonal CMT (Latour et al., 1997). The S50P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S50P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (S49P/Y, F51L, C53S/Y) have been reported in the Human Gene Mutation Database in association with CMT (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded
Athena Diagnostics Inc RCV000518090 SCV000613477 uncertain significance not specified 2016-12-02 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789248 SCV000928600 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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