Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000524063 | SCV000619848 | likely pathogenic | not provided | 2017-08-07 | criteria provided, single submitter | clinical testing | The c.378dupG variant causes a frameshift starting with codon Leucine 127, changes this amino acid to a Alanine residue and creates a premature Stop codon at position 132 of the new reading frame, denoted p.Leu127AlafsX132. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.378dupG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the c.378dupG variant has not been reported previously to our knowledge, other loss-of-function variants in the CLCN1 gene have been reported in the Human Gene Mutation Database in association with CLCN1-related disorders (Stenson et al., 2014). |
Labcorp Genetics |
RCV001853654 | SCV002238151 | pathogenic | Congenital myotonia, autosomal recessive form; Congenital myotonia, autosomal dominant form | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu127Alafs*132) 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 premature translational stop signal has been observed in individual(s) with autosomal recessive myotonia congenita or Segawa syndrome (PMID: 28427807, 28600779). This variant is also known as s as c.378_379insG and p.L126fs. ClinVar contains an entry for this variant (Variation ID: 451184). For these reasons, this variant has been classified as Pathogenic. |
Laboratory of Medical Genetics, |
RCV003883155 | SCV004697564 | pathogenic | Congenital myotonia, autosomal recessive form | 2024-02-20 | criteria provided, single submitter | clinical testing |