Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000220506 | SCV000279582 | likely pathogenic | not provided | 2016-01-21 | criteria provided, single submitter | clinical testing | The C179Y variant in the GJB1 gene has been reported previously in association with Charcot-Marie-Tooth type X1 disease (CMTX1) (Casasnovas et al., 2006). The C179Y variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C179Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. This substitution occurs at a position that is conserved across species. Different missense variants in the same codon (C179G/R) as well as multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with GJB1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. This variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Gene |
RCV000020175 | SCV000040506 | pathologic | Charcot-Marie-Tooth Neuropathy X Type 1 | 2010-04-15 | no assertion criteria provided | curation | Converted during submission to Pathogenic. |
| Inherited Neuropathy Consortium | RCV000789199 | SCV000928551 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |