ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.742A>T (p.Lys248Ter)

gnomAD frequency: 0.00002  dbSNP: rs561470261
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760440 SCV000890323 pathogenic not provided 2023-03-02 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25487368, 17654559, 31589614, 22246887)
Labcorp Genetics (formerly Invitae), Labcorp RCV001223937 SCV001396108 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys248*) 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 present in population databases (rs561470261, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 22246887, 25487368). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 620142). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000760440 SCV002019326 pathogenic not provided 2020-12-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001223937 SCV005667214 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2024-01-02 criteria provided, single submitter clinical testing

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