Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011204 | SCV001171500 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-26 | criteria provided, single submitter | clinical testing | The p.T46S variant (also known as c.136A>T), located in coding exon 1 of the TMEM127 gene, results from an A to T substitution at nucleotide position 136. The threonine at codon 46 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001058899 | SCV001223497 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2021-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with serine at codon 46 of the TMEM127 protein (p.Thr46Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. 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. 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, 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 TMEM127-related conditions. |