Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001056057 | SCV001220476 | uncertain significance | Lower motor neuron syndrome with late-adult onset; Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; Autosomal dominant mitochondrial myopathy with exercise intolerance | 2019-03-23 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces arginine with histidine at codon 15 of the CHCHD10 protein (p.Arg15His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant has not been reported in the literature in individuals with CHCHD10-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg15 amino acid residue in CHCHD10. Other variant(s) that disrupt this residue (p.Arg15Leu) have been determined to be pathogenic (PMID: 25113787, 25261972, 25681414, 28585542, 29121267, 29315381, 29789341). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). |