Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002029841 | SCV002115928 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2021-04-17 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function. This variant has not been reported in the literature in individuals with SDHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with lysine at codon 227 of the SDHB protein (p.Thr227Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine. |
| Ambry Genetics | RCV004038732 | SCV005019681 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-28 | criteria provided, single submitter | clinical testing | The p.T227K variant (also known as c.680C>A), located in coding exon 7 of the SDHB gene, results from a C to A substitution at nucleotide position 680. The threonine at codon 227 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |