Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001961375 | SCV002254761 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2020-12-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals with SDHB-related conditions. This sequence change replaces methionine with isoleucine at codon 133 of the SDHB protein (p.Met133Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |
| Ambry Genetics | RCV002352672 | SCV002622605 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.M133I variant (also known as c.399G>T), located in coding exon 4 of the SDHB gene, results from a G to T substitution at nucleotide position 399. The methionine at codon 133 is replaced by isoleucine, 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. |