Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000530563 | SCV000637916 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2019-02-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Gln157*) that lies downstream of this variant has been determined to be pathogenic (PMID: 22419703, Invitae). This suggests that deletion of this region of the TMEM127 protein is causative of disease. This variant has been observed in an individual affected with bilateral pheochromocytoma (PMID: 20154675). This variant is also known as c.264_267delCAGA in the literature. ClinVar contains an entry for this variant (Variation ID: 126966). 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.Thr89Cysfs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 150 amino acids of the TMEM127 protein. |
| Ambry Genetics | RCV002453425 | SCV002739427 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-04 | criteria provided, single submitter | clinical testing | The c.265_268delACAG pathogenic mutation, located in coding exon 2 of the TMEM127 gene, results from a deletion of 4 nucleotides at nucleotide positions 265 to 268, causing a translational frameshift with a predicted alternate stop codon (p.T89Cfs*34). This alteration occurs near the 3' terminus of the TMEM127 gene and is not expected to trigger nonsense-mediated mRNA decay; however, this impacts the last 117 amino acids of the protein. Premature stop codons are typically deleterious in nature and this variant has been reported in an individual diagnosed with bilateral pheochromocytomas at age 46 (Yao L et al. JAMA. 2010 Dec;304:2611-9). This variant has also been seen in individuals with early onset pheochromocytomas and/or features consistent with PGL/PCC syndrome (Internal Ambry data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV000114825 | SCV004206188 | pathogenic | Pheochromocytoma | 2023-04-27 | criteria provided, single submitter | clinical testing | |
| Familial Cancer Clinic, |
RCV000114825 | SCV000148720 | likely pathogenic - adrenal bilateral pheochromocy | Pheochromocytoma | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |