ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.411delinsGGA (p.Tyr137Ter)

dbSNP: rs1586484463
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000991826 SCV001143599 likely pathogenic not provided 2018-12-31 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. The best available variant frequency is uninformative because there are too few occurrences in population data.
Invitae RCV001247973 SCV001421429 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-01-12 criteria provided, single submitter clinical testing 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). This variant has not been reported in the literature in individuals with CLCN1-related conditions, however, a different variant (c.411C>G) giving rise to the same protein effect observed here (p.Tyr137*) has been reported in combination with another CLCN1 variant in a family affected with myotonia congenita (PMID: 18337730). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr137*) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product.
GeneDx RCV000991826 SCV001829657 pathogenic not provided 2019-04-15 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29606556, 18337730)

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