Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546329 | SCV000636296 | pathogenic | Congenital myotonia, autosomal recessive form | 2017-03-26 | criteria provided, single submitter | clinical testing | This sequence change deletes 1 nucleotide in exon 4 of the CLCN1 mRNA (c.469delC), causing a frameshift at codon 157. This creates a premature translational stop signal (p.Leu157Phefs*13) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in CLCN1 are known to cause autosomal recessive forms of myotonia congenita (PMID: 17932099, 22094069, 23739125). For these reasons, this variant has been classified as Pathogenic. |
| Invitae | RCV001382363 | SCV001581102 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-09-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu157Phefs*13) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 462831). For these reasons, this variant has been classified as Pathogenic. |