Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001756513 | SCV001985329 | uncertain significance | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 20197121, 27484306, 26475597, 33300680) |
Labcorp Genetics |
RCV002032768 | SCV002175789 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2023-02-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1303014). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 46 of the SUCLG1 protein (p.Ser46Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with mitochondrial DNA depletion syndrome (PMID: 20197121, 26475597). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SUCLG1 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. |