Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000233811 | SCV000288149 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 233 of the SDHA protein (p.Gly233Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SDH-deficient gastrointestinal stromal tumors (PMID: 35059314). ClinVar contains an entry for this variant (Variation ID: 239681). 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 expected to disrupt SDHA protein function with a positive predictive value of 80%. 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. |
| “Giorgio Prodi” Cancer Research Center, |
RCV001799644 | SCV002026141 | uncertain significance | Gastrointestinal stromal tumor | 2021-10-01 | criteria provided, single submitter | research | |
| Ambry Genetics | RCV002372275 | SCV002668029 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-21 | criteria provided, single submitter | clinical testing | The p.G233V variant (also known as c.698G>T), located in coding exon 6 of the SDHA gene, results from a G to T substitution at nucleotide position 698. The glycine at codon 233 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Mayo Clinic Laboratories, |
RCV003480563 | SCV004227049 | uncertain significance | not provided | 2023-02-21 | criteria provided, single submitter | clinical testing | PP3, PM3 |