Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001203949 | SCV001375134 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2019-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with cysteine at codon 173 of the TMEM127 protein (p.Phe173Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is not present in population databases (ExAC no frequency). 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 (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 | RCV002339511 | SCV002644169 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-26 | criteria provided, single submitter | clinical testing | The p.F173C variant (also known as c.518T>G), located in coding exon 3 of the TMEM127 gene, results from a T to G substitution at nucleotide position 518. The phenylalanine at codon 173 is replaced by cysteine, an amino acid with highly 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. |