ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.378dup (p.Leu127fs)

dbSNP: rs1320040467
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000524063 SCV000619848 likely pathogenic not provided 2017-08-07 criteria provided, single submitter clinical testing The c.378dupG variant causes a frameshift starting with codon Leucine 127, changes this amino acid to a Alanine residue and creates a premature Stop codon at position 132 of the new reading frame, denoted p.Leu127AlafsX132. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.378dupG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the c.378dupG 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 RCV001853654 SCV002238151 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-11-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu127Alafs*132) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive myotonia congenita or Segawa syndrome (PMID: 28427807, 28600779). This variant is also known as s as c.378_379insG and p.L126fs. ClinVar contains an entry for this variant (Variation ID: 451184). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV003883155 SCV004697564 pathogenic Congenital myotonia, autosomal recessive form 2024-02-20 criteria provided, single submitter clinical testing

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