Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000233573 | SCV000288120 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 553 of the SDHA protein (p.Asp553Asn). This variant is present in population databases (rs769882609, gnomAD 0.007%). This missense change has been observed in individual(s) with epitheloid sarcoma (PMID: 28878254). ClinVar contains an entry for this variant (Variation ID: 239654). 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 | RCV001012585 | SCV001173055 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-10 | criteria provided, single submitter | clinical testing | The p.D553N variant (also known as c.1657G>A), located in coding exon 12 of the SDHA gene, results from a G to A substitution at nucleotide position 1657. The aspartic acid at codon 553 is replaced by asparagine, an amino acid with highly similar properties. In a study of Asian patients with sporadic sarcomas, this alteration was detected in one patient diagnosed with an epitheloid sarcoma at age 24 (Chan SH et al. Sci Rep, 2017 Sep;7:10660). 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. |
Gene |
RCV001762530 | SCV002007980 | uncertain significance | not provided | 2023-08-21 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with a sarcoma (Chan et al., 2017); This variant is associated with the following publications: (PMID: 28878254) |
Baylor Genetics | RCV003475072 | SCV004202392 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-10-11 | criteria provided, single submitter | clinical testing |