Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001035732 | SCV001199066 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2022-11-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminal domain of the MAX protein, which is essential for protein localization to the nucleus and suppression of MYC transactivation activity (PMID: 1459463, 1730412, 7630640). While functional studies have not been performed to directly test the effect of this variant on MAX protein function, this suggests that disruption of this region of the protein is causative of disease. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 834944). Disruption of this splice site has been observed in individuals with paraganglioma and pheochromocytoma (PMID: 21685915, 22452945). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the MAX gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |