ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2403+5G>A

gnomAD frequency: 0.00001  dbSNP: rs1474520642
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498136 SCV000589730 likely pathogenic not provided 2016-01-25 criteria provided, single submitter clinical testing Although the c.1266+2 T>C variant has not been reported as a pathogenic variant or as a benign variant to our knowledge, it destroys the canonical splice donor site in intron 10 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site variants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.1266+2 T>C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.1266+2 T>C in the DSP gene is expected to be pathogenic
Labcorp Genetics (formerly Invitae), Labcorp RCV000689048 SCV000816685 likely pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-11-19 criteria provided, single submitter clinical testing This sequence change falls in intron 20 of the CLCN1 gene. It does not directly change the encoded amino acid sequence of the CLCN1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has been observed in individual(s) with clinical features of myotonia congenita (Invitae; external communication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 432056). 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. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.