Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001060989 | SCV001225711 | uncertain significance | Hereditary spastic paraplegia 43 | 2019-05-03 | criteria provided, single submitter | clinical testing | 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.Gly66 amino acid residue in C19orf12. Other variant(s) that disrupt this residue have been observed in individuals with C19orf12-related conditions (PMID: 22584950), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with C19orf12-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 66 of the C19orf12 protein (p.Gly66Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |