ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2017_2018del (p.Ala673fs)

dbSNP: rs1586515112
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008934 SCV001168741 likely pathogenic not provided 2018-07-10 criteria provided, single submitter clinical testing The c.2017_2018delGC variant is not observed in large population cohorts (Lek et al., 2016). The c.2017_2018delGC variant causes a frameshift starting with codon Alanine 673, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 40 of the new reading frame, denoted p.Ala673SerfsX40. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although the c.2017_2018delGC variant has not been reported previously to our knowledge, other loss-of-function variants in the CLCN1 gene have been reported in the Human Gene Mutation Database in association with CLCN1-related disorders (Stenson et al., 2014).
Labcorp Genetics (formerly Invitae), Labcorp RCV001035266 SCV001198589 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-03-07 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala673Serfs*40) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CLCN1-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125).

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