ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.774G>A (p.Glu258=) (rs770605959)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kariminejad - Najmabadi Pathology & Genetics Center RCV000788076 SCV000927074 uncertain significance Myotonia 2018-11-17 criteria provided, single submitter clinical testing
Invitae RCV001063540 SCV001228390 uncertain significance Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2019-12-06 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 of the CLCN1 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs770605959, ExAC 0.001%). This variant has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 28427807). This variant is also known as c.861G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 636302). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. 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.

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