Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570081 | SCV000674942 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-24 | criteria provided, single submitter | clinical testing | The p.Y141D variant (also known as c.421T>G), located in coding exon 4 of the SDHA gene, results from a T to G substitution at nucleotide position 421. The tyrosine at codon 141 is replaced by aspartic acid, an amino acid with highly dissimilar 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. |
| Invitae | RCV001342949 | SCV001536901 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 141 of the SDHA protein (p.Tyr141Asp). This variant is not present in population databases (gnomAD no frequency). 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: 486360). 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. |