Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038662 | SCV001202141 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2022-08-31 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 837349). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is present in population databases (rs763547482, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 83 of the SDHB protein (p.Val83Gly). |