ClinVar Miner

Submissions for variant NM_000083.3(CLCN1):c.2172+1G>T

gnomAD frequency: 0.00001  dbSNP: rs1273524525
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000693331 SCV000821196 pathogenic Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form 2023-01-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 572040). Disruption of this splice site has been observed in individual(s) with myotonia congenita (PMID: 15116370; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change affects a donor splice site in intron 17 of the CLCN1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. Studies have shown that disruption of this splice site results in skipping of exon 17 and introduces a premature termination codon (PMID: 15116370). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091924 SCV001248213 pathogenic not provided 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV001091924 SCV004030605 pathogenic not provided 2023-03-28 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 24452722, 15116370, 33464536, 27415035)

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.