Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000227862 | SCV000288150 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 242 of the SDHA protein (p.Gly242Arg). This variant is present in population databases (rs764534044, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 239682). 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 SDHA 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 | RCV001026197 | SCV001188532 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-13 | criteria provided, single submitter | clinical testing | The p.G242R variant (also known as c.724G>A), located in coding exon 6 of the SDHA gene, results from a G to A substitution at nucleotide position 724. The glycine at codon 242 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003475077 | SCV004200616 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-07-21 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477823 | SCV004220318 | uncertain significance | not provided | 2023-05-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000008 (2/251184 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |