Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011674 | SCV001172022 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-14 | criteria provided, single submitter | clinical testing | The p.P486L variant (also known as c.1457C>T), located in coding exon 11 of the SDHA gene, results from a C to T substitution at nucleotide position 1457. The proline at codon 486 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001860678 | SCV002294409 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-01-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 486 of the SDHA protein (p.Pro486Leu). ClinVar contains an entry for this variant (Variation ID: 819264). 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. 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. |