Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001035546 | SCV001198875 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2020-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 162 of the TMEM127 protein (p.Lys162Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs745947594, ExAC 0.02%). This variant has not been reported in the literature in individuals with TMEM127-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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 | RCV002337083 | SCV002639380 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-16 | criteria provided, single submitter | clinical testing | The p.K162R variant (also known as c.485A>G), located in coding exon 3 of the TMEM127 gene, results from an A to G substitution at nucleotide position 485. The lysine at codon 162 is replaced by arginine, an amino acid with highly 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. |