ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2786C>T (p.Thr929Ile) (rs777708543)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000270859 SCV000467136 uncertain significance Myotonia congenita 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000414193 SCV000491739 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLCN1 gene. The T929I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. 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. The T929I 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. Additionally, a missense variant in a nearby residue (P932L) has been reported in the Human Gene Mutation Database in association with Myotonia (Stenson et al., 2014). However, this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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