Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001372333 | SCV001568964 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2020-06-01 | 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. This variant disrupts the p.Gly96Asp amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: PMID: 16317055, 17538171, 19075037, 28891197, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 glycine with valine at codon 96 of the SDHB protein (p.Gly96Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |