Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003517124 | SCV004292624 | likely pathogenic | Hereditary pheochromocytoma-paraganglioma | 2023-02-15 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 2 of the TMEM127 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMEM127 are known to be pathogenic (PMID: 20154675, 21156949). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with pheochromocytomas (PMID: 20154675). This variant is also known as IVS2-1G>T. ClinVar contains an entry for this variant (Variation ID: 109). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Gene |
RCV004700172 | SCV005202019 | likely pathogenic | not provided | 2023-10-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 20154675, 21156949) |
| OMIM | RCV000000129 | SCV000020272 | risk factor | Pheochromocytoma, susceptibility to | 2010-03-01 | no assertion criteria provided | literature only | |
| Familial Cancer Clinic, |
RCV000114824 | SCV000148719 | likely pathogenic - adrenal pheochromocytoma | Pheochromocytoma | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |