Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001312656 | SCV001503118 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2021-09-15 | 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 expected to disrupt SDHB protein function. ClinVar contains an entry for this variant (Variation ID: 1013986). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 91 of the SDHB protein (p.Arg91Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. |
| Ambry Genetics | RCV002437069 | SCV002743640 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.R91K variant (also known as c.272G>A), located in coding exon 3 of the SDHB gene, results from a G to A substitution at nucleotide position 272. The arginine at codon 91 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |