Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000555083 | SCV000651406 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 591 of the SDHA protein (p.Ala591Val). This variant is present in population databases (rs367621815, gnomAD 0.004%). This missense change has been observed in individual(s) with head and neck paraganglioma (PMID: 30050099). ClinVar contains an entry for this variant (Variation ID: 472355). Invitae Evidence 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 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. |
| Ambry Genetics | RCV001013062 | SCV001173599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-08 | criteria provided, single submitter | clinical testing | The p.A591V variant (also known as c.1772C>T), located in coding exon 13 of the SDHA gene, results from a C to T substitution at nucleotide position 1772. The alanine at codon 591 is replaced by valine, an amino acid with similar properties. This variant has been identified in a patient with a head and neck paraganglioma from a cohort of 391 paraganglioma and/or pheochromocytoma patients (Richter S et al. Genet Med, 2019 03;21:705-717).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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002252166 | SCV002523975 | uncertain significance | See cases | 2021-04-08 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PP3 |
| Baylor Genetics | RCV003476309 | SCV004202397 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-10-09 | criteria provided, single submitter | clinical testing |