Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000114829 | SCV001135916 | pathogenic | Pheochromocytoma | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002512592 | SCV003524701 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 3 of the TMEM127 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with pheochromocytoma (PMID: 20154675, 25389632). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 107). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a new termination codon (Invitae). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000114829 | SCV003807873 | pathogenic | Pheochromocytoma | 2023-02-10 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 strong, PS4 strong, PM2 moderated |
OMIM | RCV000000127 | SCV000020270 | risk factor | Pheochromocytoma, susceptibility to | 2010-03-01 | no assertion criteria provided | literature only | |
Familial Cancer Clinic, |
RCV000114829 | SCV000148724 | likely pathogenic - adrenal pheochromocytoma | Pheochromocytoma | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |