Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463083 | SCV000553853 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-06-19 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 412341). 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 threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 271 of the SDHA protein (p.Thr271Ser). |
Fulgent Genetics, |
RCV000765827 | SCV000897222 | uncertain significance | Leigh syndrome; Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001775822 | SCV002012847 | uncertain significance | not provided | 2019-05-12 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002418426 | SCV002678787 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-19 | criteria provided, single submitter | clinical testing | The p.T271S variant (also known as c.812C>G), located in coding exon 7 of the SDHA gene, results from a C to G substitution at nucleotide position 812. The threonine at codon 271 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |