Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069933 | SCV001235131 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 47 of the TMEM127 protein (p.Ala47Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with bilateral pheochromocytoma (PMID: 20923864). ClinVar contains an entry for this variant (Variation ID: 863062). 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. Experimental studies have shown that this missense change affects TMEM127 function (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. |
| Ambry Genetics | RCV002393335 | SCV002697840 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-05 | criteria provided, single submitter | clinical testing | The p.A47D variant (also known as c.140C>A), located in coding exon 1 of the TMEM127 gene, results from a C to A substitution at nucleotide position 140. The alanine at codon 47 is replaced by aspartic acid, an amino acid with dissimilar properties. This variant has been identified in an individual with a personal and family history of bilateral pheochromocytoma; additionally, this individual's tumor demonstrated loss of heterozygosity (LOH) at the TMEM127 locus (Burnichon N et al. Eur J Endocrinol, 2011 Jan;164:141-5; Abermil N et al. J Clin Endocrinol Metab, 2012 May;97:E805-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |