Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001047814 | SCV001211796 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2019-11-27 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 219 of the TMEM127 protein (p.Pro219Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. |
| Ambry Genetics | RCV003380815 | SCV004090006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | The p.P219R variant (also known as c.656C>G), located in coding exon 3 of the TMEM127 gene, results from a C to G substitution at nucleotide position 656. The proline at codon 219 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |