Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019492 | SCV001180858 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | The p.S109P variant (also known as c.325T>C), located in coding exon 2 of the TMEM127 gene, results from a T to C substitution at nucleotide position 325. The serine at codon 109 is replaced by proline, an amino acid with similar properties. This alteration was identified in multiple individuals diagnosed with head/neck paragangliomas (Neumann HP et al. J. Clin. Endocrinol. Metab., 2011 Aug;96:E1279-82; Bausch B. JAMA Oncol. 2017 Sep;3(9):1204-1212). This amino acid position is well 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. |
Invitae | RCV001237919 | SCV001410708 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 109 of the TMEM127 protein (p.Ser109Pro). This variant is present in population databases (rs761032675, gnomAD 0.003%). This missense change has been observed in individual(s) with paraganglioma (PMID: 21613359, 28384794). ClinVar contains an entry for this variant (Variation ID: 823332). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Studies have shown that this missense change alters TMEM127 gene expression (PMID: 32575117). 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. |