Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001980223 | SCV002238806 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln812*) 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 present in population databases (rs772150974, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with autosomal recessive myotonia congenita (PMID: 26096614, 32117024). This variant has been reported in individual(s) with autosomal dominant myotonia congenita (PMID: 21221019); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 1459630). For these reasons, this variant has been classified as Pathogenic. |
| MGZ Medical Genetics Center | RCV002290823 | SCV002579613 | pathogenic | Congenital myotonia, autosomal recessive form | 2021-11-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003154051 | SCV003842435 | pathogenic | not provided | 2023-03-13 | criteria provided, single submitter | clinical testing | Reported previously in an individual with myotonia congenita where a second CLCN1 variant was not identified (Modoni et al., 2011); Reported in two siblings with myotonia who harbored additional likely benign variants in the CLCN1 gene (Brugnoni et al., 2013); Nonsense variant predicted to result in protein truncation or nonsense mediated decay 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, 26510092, 32117024, 28427807, 23739125, 26096614, 21221019, 22521272) |
| Neuberg Centre For Genomic Medicine, |
RCV002290823 | SCV004176373 | pathogenic | Congenital myotonia, autosomal recessive form | 2023-02-14 | criteria provided, single submitter | clinical testing | The stop gained c.2434C>T (p.Gln812Ter) variant in CLCN1 gene has been previously reported in homozygous and compound heterozygous states in multiple individuals affected with Myotonia congenita (Imbrici et al., 2015; Brugnoni et al., 2013; Modoni et al., 2011). The p.Gln812Ter variant has been reported with allele frequency of 0.002% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). The nucleotide change c.2434C>T in CLCN1 gene is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Gln812Ter) in the CLCN1 gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in CLCN1 gene have been previously reported to be pathogenic (Brugnoni et al., 2013). For these reasons, this variant has been classified as Pathogenic |
| Fulgent Genetics, |
RCV001980223 | SCV005667257 | likely pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2024-03-06 | criteria provided, single submitter | clinical testing |