Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000703658 | SCV000832568 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2018-05-25 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-3 and part of exon 1 (c.50_434-202del) of the CLCN1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CLCN1-related disease. The observation of one or more missense substitutions within the deleted region (p.Gln43Arg, p.Asp89Gly, and p.Asp136Gly) in individuals affected with myotonia congenita suggests that this may be a clinically significant region of the CLCN1 protein (PMID: 24349310, 26502825, Invitae database). Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). For these reasons, this variant has been classified as Pathogenic. |