Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002335825 | SCV002644085 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | The p.Y169C variant (also known as c.506A>G), located in coding exon 5 of the SDHA gene, results from an A to G substitution at nucleotide position 506. The tyrosine at codon 169 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
| Invitae | RCV003096600 | SCV002978198 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-04-16 | 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 present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 169 of the SDHA protein (p.Tyr169Cys). ClinVar contains an entry for this variant (Variation ID: 1745142). 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) 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. |
| Baylor Genetics | RCV004572297 | SCV005055616 | uncertain significance | Dilated cardiomyopathy 1GG | 2024-02-16 | criteria provided, single submitter | clinical testing |