Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000649400 | SCV000771228 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 560 of the SDHA protein (p.Thr560Met). This variant is present in population databases (rs775350508, gnomAD 0.005%). 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: 539635). 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. |
Ambry Genetics | RCV001012616 | SCV001173092 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-27 | criteria provided, single submitter | clinical testing | The p.T560M variant (also known as c.1679C>T), located in coding exon 13 of the SDHA gene, results from a C to T substitution at nucleotide position 1679. The threonine at codon 560 is replaced by methionine, 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. |
Gene |
RCV003313127 | SCV004012368 | uncertain significance | not provided | 2023-07-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 34870338) |
Baylor Genetics | RCV003472040 | SCV004200598 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-08-14 | criteria provided, single submitter | clinical testing | |
Genome |
RCV000649400 | SCV001749694 | not provided | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 09-26-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |