Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000548237 | SCV000651374 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-11-20 | 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 453 of the SDHA protein (p.Gly453Arg). This variant is present in population databases (rs770028533, gnomAD 0.004%). 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: 472324). 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 | RCV001011154 | SCV001171443 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-01 | criteria provided, single submitter | clinical testing | The p.G453R variant (also known as c.1357G>A), located in coding exon 10 of the SDHA gene, results from a G to A substitution at nucleotide position 1357. The glycine at codon 453 is replaced by arginine, an amino acid with dissimilar properties. This alteration was previously identified as a somatic finding in a gastrointestinal stromal tumor (GIST) demonstrating absence of SDHB and presence of SDHA protein staining by IHC; however, this alteration was not detected in the germline of this individual (Belinsky MG et al. Genes Chromosomes Cancer, 2013 Feb;52:214-24). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003476308 | SCV004202373 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-10-26 | criteria provided, single submitter | clinical testing |