Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000226409 | SCV000288101 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 399 of the SDHA protein (p.Pro399Leu). This variant is present in population databases (no rsID available, 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: 239638). 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. |
| Counsyl | RCV000663203 | SCV000786383 | uncertain significance | Paragangliomas 5 | 2018-04-25 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001010179 | SCV001170336 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-25 | criteria provided, single submitter | clinical testing | The p.P399L variant (also known as c.1196C>T), located in coding exon 9 of the SDHA gene, results from a C to T substitution at nucleotide position 1196. The proline at codon 399 is replaced by leucine, an amino acid with similar properties. 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. |
| Myriad Genetics, |
RCV000663203 | SCV004045411 | uncertain significance | Paragangliomas 5 | 2023-04-21 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |