ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.423C>G (p.Phe141Leu) (rs1555937180)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519658 SCV000617391 likely pathogenic not provided 2017-11-02 criteria provided, single submitter clinical testing The F141L variant was initially reported in the hemizygous state in an individual with Charcot-Marie-Tooth disease (CMT) (Rouger et al., 1997). Subsequently, F141L was reported in additional families with CMT, although detailed clinical information and segregation analysis was not provided (Birouk et al., 1998; Dubourg et al., 2001). The F141L variant is not observed in large population cohorts (Lek et al., 2016). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and missense variants in nearby residues (V139M; R142Q/W) 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. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Inherited Neuropathy Consortium RCV000789935 SCV000929320 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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