Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001921498 | SCV002203367 | uncertain significance | Pyruvate dehydrogenase E3 deficiency | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 458 of the DLD protein (p.Pro458Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs779723449, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with DLD-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |