Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001235932 | SCV001408641 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2019-10-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TMEM127-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with leucine at codon 187 of the TMEM127 protein (p.Ser187Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. 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. 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 | RCV002348795 | SCV002651438 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-01 | criteria provided, single submitter | clinical testing | The p.S187L variant (also known as c.560C>T), located in coding exon 3 of the TMEM127 gene, results from a C to T substitution at nucleotide position 560. The serine at codon 187 is replaced by leucine, an amino acid with dissimilar properties. 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. |