Total submissions: 3
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. |
Ce |
RCV001091924 | SCV001248213 | pathogenic | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Gene |
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) |