Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000700721 | SCV000829489 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-08-16 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 577865). This missense change has been observed in individual(s) with pheochromocytoma (PMID: 30877234, 33051659). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 186 of the TMEM127 protein (p.Ala186Pro). |
Ambry Genetics | RCV002343526 | SCV002650915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-16 | criteria provided, single submitter | clinical testing | The p.A186P variant (also known as c.556G>C), located in coding exon 3 of the TMEM127 gene, results from a G to C substitution at nucleotide position 556. The alanine at codon 186 is replaced by proline, an amino acid with highly similar properties. This alteration has been identified in multiple individuals diagnosed with pheochromocytoma (Ben Aim L et al. J Med Genet, 2019 Aug;56:513-520; Armaiz-Pena G et al. J Clin Endocrinol Metab, 2021 Jan;106:e350-e364). 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. |
Baylor Genetics | RCV004569363 | SCV005054302 | uncertain significance | Pheochromocytoma | 2024-02-05 | criteria provided, single submitter | clinical testing |