Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164900 | SCV000215587 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-15 | criteria provided, single submitter | clinical testing | The p.Q159* pathogenic mutation (also known as c.475C>T), located in coding exon 3 of the TMEM127 gene, results from a C to T substitution at nucleotide position 475. This alteration occurs at the 3' terminus of theTMEM127 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 80 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This alteration has been reported in a family with multiple family members diagnosed with bilateral pheochromocytomas from 48y to 72y (Qin Y et al. Nat Genet. 2010 Mar; 42(3):229-33). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV001381352 | SCV001579708 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2020-10-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the TMEM127 protein. Other variant(s) that disrupt this region (p.Tyr178Leufs*48) have been determined to be pathogenic (PMID: 28855235, 28384794). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in individual(s) with paraganglioma-pheochromocytoma syndrome (PMID: 20154675). ClinVar contains an entry for this variant (Variation ID: 108). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the TMEM127 gene (p.Gln159*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acids of the TMEM127 protein. |
| OMIM | RCV000000128 | SCV000020271 | risk factor | Pheochromocytoma, susceptibility to | 2010-03-01 | no assertion criteria provided | literature only | |
| Familial Cancer Clinic, |
RCV000114833 | SCV000148728 | likely pathogenic - adrenal bilateral pheochromocy | Pheochromocytoma | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |