ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.774G>A (p.Glu258=)

gnomAD frequency: 0.00001  dbSNP: rs770605959
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kariminejad - Najmabadi Pathology & Genetics Center RCV001836882 SCV000927074 likely pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
Invitae RCV001063540 SCV001228390 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-12-10 criteria provided, single submitter clinical testing This sequence change affects codon 258 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 also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. This variant is present in population databases (rs770605959, gnomAD 0.0009%). This variant has been observed in individuals with autosomal recessive myotonia congenita (PMID: 28427807; Invitae). This variant is also known as c.861G>A. ClinVar contains an entry for this variant (Variation ID: 636302). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV003883164 SCV004697568 likely pathogenic Congenital myotonia, autosomal recessive form 2024-02-20 criteria provided, single submitter clinical testing

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