Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000196324 | SCV000251227 | uncertain significance | not provided | 2014-04-23 | criteria provided, single submitter | clinical testing | p.Val82Met (GTG>ATG): c.244 G>A in exon 2 of the C12ORF65 gene (NM_152269.4)A variant of unknown significance has been identified in the C12ORF65 gene. The V82M variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V82M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in this gene have not been reported as pathogenic. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s). |
Labcorp Genetics |
RCV002228874 | SCV002509516 | uncertain significance | Combined oxidative phosphorylation defect type 7; Spastic paraplegia | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 82 of the C12orf65 protein (p.Val82Met). This variant is present in population databases (rs374311195, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with C12orf65-related conditions. ClinVar contains an entry for this variant (Variation ID: 214191). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |