Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022207 | SCV001183915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-25 | criteria provided, single submitter | clinical testing | The p.L143M variant (also known as c.427T>A), located in coding exon 5 of the SDHB gene, results from a T to A substitution at nucleotide position 427. The leucine at codon 143 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001070335 | SCV001235558 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with methionine at codon 143 of the SDHB protein (p.Leu143Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. 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 tolerated. 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. |