Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649402 | SCV000771230 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-08-03 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 539637). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is present in population databases (rs60587941, gnomAD 0.006%). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 654 of the SDHA protein (p.Cys654Gly). |
| Ambry Genetics | RCV003162970 | SCV003855163 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-10 | criteria provided, single submitter | clinical testing | The p.C654G variant (also known as c.1960T>G), located in coding exon 15 of the SDHA gene, results from a T to G substitution at nucleotide position 1960. The cysteine at codon 654 is replaced by glycine, an amino acid with highly 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. |