Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000662906 | SCV000785828 | uncertain significance | Paragangliomas 5 | 2017-12-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000818760 | SCV000959391 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 281 of the SDHA protein (p.Thr281Ala). This variant is present in population databases (rs772325115, gnomAD 0.008%). 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: 548821). 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 with a negative predictive value of 95%. 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 | RCV002442385 | SCV002679390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-21 | criteria provided, single submitter | clinical testing | The p.T281A variant (also known as c.841A>G), located in coding exon 7 of the SDHA gene, results from an A to G substitution at nucleotide position 841. The threonine at codon 281 is replaced by alanine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002493076 | SCV002791151 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy | 2021-10-06 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV000662906 | SCV004018578 | uncertain significance | Paragangliomas 5 | 2023-04-20 | 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. |
| Prevention |
RCV003420161 | SCV004118549 | uncertain significance | SDHA-related condition | 2022-10-26 | criteria provided, single submitter | clinical testing | The SDHA c.841A>G variant is predicted to result in the amino acid substitution p.Thr281Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-231061-A-G) and has been interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/548821/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003472060 | SCV004200612 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-07-27 | criteria provided, single submitter | clinical testing |