Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000819929 | SCV000960616 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2023-07-28 | 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) 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. ClinVar contains an entry for this variant (Variation ID: 662316). 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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 450 of the SDHA protein (p.Asn450Ser). |
| Ambry Genetics | RCV002381857 | SCV002693343 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-28 | criteria provided, single submitter | clinical testing | The p.N450S variant (also known as c.1349A>G), located in coding exon 10 of the SDHA gene, results from an A to G substitution at nucleotide position 1349. The asparagine at codon 450 is replaced by serine, an amino acid with highly 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. |
| Baylor Genetics | RCV003473505 | SCV004200613 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-07-23 | criteria provided, single submitter | clinical testing |