Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129940 | SCV000184759 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-12-24 | criteria provided, single submitter | clinical testing | The p.R75* pathogenic mutation (also known as c.223C>T), located in coding exon 4 of the MAX gene, results from a C to T substitution at nucleotide position 223. This changes the amino acid from an arginine to a stop codon within coding exon 4. This mutation was originally identified in a family with multiple cases of early-onset bilateral pheochromocytomas (PCC); the PCC tumor of the proband demonstrated absent immunohistochemical staining and loss of heterozygosity for MAX (Comino-Méndez I et al. Nat. Genet., 2011 Jun;43:663-7). This pathogenic variant was also described in other individuals with bilateral PCC (Burnichon N et al. Clin. Cancer Res., 2012 May;18:2828-37; Pczkowska M et al. Clin. Endocrinol. (Oxf), 2013 Dec;79:817-23). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV000524813 | SCV000637870 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2022-11-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 29786). This premature translational stop signal has been observed in individual(s) with bilateral adrenal pheochromoytoma and adrenal pheochromocytoma (PMID: 21685915, 22452945, 23551045). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs387906650, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Arg75*) in the MAX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MAX are known to be pathogenic (PMID: 21685915, 26070438). |
| OMIM | RCV000022653 | SCV000043942 | risk factor | Pheochromocytoma, susceptibility to | 2011-06-19 | no assertion criteria provided | literature only |