ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.187G>A (p.Val63Ile) (rs116840818)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217618 SCV000278980 pathogenic not provided 2018-05-23 criteria provided, single submitter clinical testing The V63I missense variant in the GJB1 gene has been reported previously in association with CMTX1 (Fairweather et al., 1994; Hoyer et al., 2014) and is associated with a mild to moderate clinical presentation in both males and females (Deschenes et al., 1997). Functional studies in murine cells demonstrate that at least some of the V63I variant protein is able to localize to the cell surface, show no significant effect on the ability of the mutant protein to form gap junctions, and to date have failed to elucidate the pathogenic mechanism of the V63I mutant protein (Deschenes et al., 1997; Wang et al., 2003). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In addition, this substitution occurs at a position that is highly conserved across species and many other missense variants are reported in this region of the protein (Stenson et al., 2014). Therefore the presence of the V63I pathogenic variant is consistent with a diagnosis of CMTX1
Athena Diagnostics Inc RCV000217618 SCV000613479 pathogenic not provided 2016-03-30 criteria provided, single submitter clinical testing
GeneReviews RCV000020171 SCV000040500 pathologic X-linked hereditary motor and sensory neuropathy 2010-04-15 no assertion criteria provided curation Converted during submission to Pathogenic.
Inherited Neuropathy Consortium RCV000789665 SCV000929039 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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