Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813402 | SCV000953761 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 255 of the SDHB protein (p.Lys255Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paraganglioma (PMID: 19454582, 34906457). ClinVar contains an entry for this variant (Variation ID: 656886). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV004028790 | SCV005019712 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-26 | criteria provided, single submitter | clinical testing | The p.K255E variant (also known as c.763A>G), located in coding exon 7 of the SDHB gene, results from an A to G substitution at nucleotide position 763. The lysine at codon 255 is replaced by glutamic acid, an amino acid with similar properties. This variant has been reported in paraganglioma/pheochromocytoma cohorts (Burnichon N et al. J Clin Endocrinol Metab, 2009 Aug;94:2817-27; Garrett A et al. Genet Med, 2022 Jan;24:41-50). 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. |