ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.1283T>C (p.Phe428Ser) (rs774843953)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518351 SCV000612759 pathogenic not provided 2019-02-19 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function.
Invitae RCV000701519 SCV000830322 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2018-07-02 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 428 of the CLCN1 protein (p.Phe428Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs774843953, ExAC 0.001%). This variant has been observed in an individual affected with paramyotonia congenita (PMID: 12390967). ClinVar contains an entry for this variant (Variation ID: 208083). Experimental studies have shown that this missense variant results in chloride channels with gating properties similar to wild type. However, cells expressing this variant had reduced expression resulting in significantly reduced absolute current amplitude (PMID: 12390967). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000518351 SCV000858401 uncertain significance not provided 2017-11-28 criteria provided, single submitter clinical testing
GeneReviews RCV000193137 SCV000243884 pathogenic Myotonia congenita 2015-08-06 no assertion criteria provided literature only

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