Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002006868 | SCV002293807 | uncertain significance | Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 5 of the SUCLA2 protein (p.Met5Ile). This variant is present in population databases (rs199738859, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SUCLA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1506628). 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 isoleucine 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. |
| Ambry Genetics | RCV002545483 | SCV003702515 | uncertain significance | Inborn genetic diseases | 2022-04-27 | criteria provided, single submitter | clinical testing | The c.15G>A (p.M5I) alteration is located in exon 1 (coding exon 1) of the SUCLA2 gene. This alteration results from a G to A substitution at nucleotide position 15, causing the methionine (M) at amino acid position 5 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |