ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.409T>G (p.Tyr137Asp) (rs748639603)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692856 SCV000820701 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2018-06-04 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with aspartic acid at codon 137 of the CLCN1 protein (p.Tyr137Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is present in population databases (rs748639603, ExAC 0.009%). This variant has been observed in several individuals affected with myotonia congenita (PMID: 22094069, 26502825). Experimental studies have shown that this missense change results in altered calcium channel function as well as reduced channel insertion into the surface membrane (PMID: 22094069, 26502825). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Athena Diagnostics Inc RCV000991825 SCV001143598 pathogenic not provided 2018-12-31 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because it is below the disease allele frequency. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Occurs in three or more cases with a recessive pathogenic variant in the same gene. Damaging to protein function(s) relevant to disease mechanism.

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