Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556956 | SCV000651475 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 329 of the SDHA protein (p.Arg329Gly). This variant is present in population databases (rs771328239, 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: 472422). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SDHA protein function with a negative predictive value of 95%. 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 | RCV002384224 | SCV002693214 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-10 | criteria provided, single submitter | clinical testing | The p.R329G variant (also known as c.985C>G), located in coding exon 8 of the SDHA gene, results from a C to G substitution at nucleotide position 985. The arginine at codon 329 is replaced by glycine, 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. |