ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1663C>T (p.His555Tyr) (rs201850090)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000437007 SCV000533714 likely pathogenic not provided 2017-06-13 criteria provided, single submitter clinical testing The H555Y variant in the CLCN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The H555Y variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The H555Y 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in the same (H555N) and nearby residues (T550M/R; G551D; I553F; H555N; I556N; M560T) have been reported in the Human Gene Mutation Database in association with myotonia congenita (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret H555Y as a likely pathogenic variant.

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