Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021678 | SCV001183325 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-20 | criteria provided, single submitter | clinical testing | The p.I134N variant (also known as c.401T>A), located in coding exon 2 of the TMEM127 gene, results from a T to A substitution at nucleotide position 401. The isoleucine at codon 134 is replaced by asparagine, an amino acid with dissimilar 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 | RCV001242437 | SCV001415524 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2019-10-29 | 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 disruptive, 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 isoleucine with asparagine at codon 134 of the TMEM127 protein (p.Ile134Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. |