ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.264G>A (p.Val88=) (rs759188441)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558306 SCV000636320 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-04-12 criteria provided, single submitter clinical testing This sequence change affects codon 88 of the CLCN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CLCN1 protein. This variant is present in population databases (rs759188441, ExAC 0.09%). This variant has been observed to be homozygous and in combination with another CLCN1 variant in individuals affected with myotonia congenita (PMID:23152584, Invitae). ClinVar contains an entry for this variant (Variation ID: 462840). Studies have shown that muscle tissue from patients who are homozygous for this change produce CLCN1 mRNA transcripts lacking exon 2 (PMID: 23152584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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