Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130864 | SCV000185763 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-12 | criteria provided, single submitter | clinical testing | The p.H133R variant (also known as c.398A>G), located in coding exon 2 of the TMEM127 gene, results from an A to G substitution at nucleotide position 398. The histidine at codon 133 is replaced by arginine, an amino acid with highly similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with TMEM127-related disease, including one individual with bilateral pheochromocytomas and another individual with a pheochromocytoma diagnosed under age 50 (Ambry internal data; Winzeler B et al. Clin Endocrinol (Oxf), 2021 Dec;:; 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. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV000466516 | SCV000543179 | likely pathogenic | Hereditary pheochromocytoma-paraganglioma | 2024-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 133 of the TMEM127 protein (p.His133Arg). This variant is present in population databases (rs587782203, gnomAD 0.004%). This missense change has been observed in individuals with clinical features of paraganglioma-pheochromocytoma syndromes (PMID: 33051659; internal data). ClinVar contains an entry for this variant (Variation ID: 142056). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV004567123 | SCV005054290 | uncertain significance | Pheochromocytoma | 2024-03-28 | criteria provided, single submitter | clinical testing | |
| Knight Diagnostic Laboratories, |
RCV000415718 | SCV000493811 | uncertain significance | Pheochromocytoma, susceptibility to | 2015-12-04 | no assertion criteria provided | clinical testing |