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; PÄ™czkowska 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 Paraganglioma-Pheochromocytoma Syndromes | 2019-09-19 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with bilateral adrenal pheochromoytoma in a single family (PMID: 21685915), and has been reported in additional unrelated individuals with adrenal pheochromocytoma (PMID: 22452945, 23551045). ClinVar contains an entry for this variant (Variation ID: 29786). Loss-of-function variants in MAX are known to be pathogenic (PMID: 21685915, 26070438). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000022653 | SCV000043942 | risk factor | Pheochromocytoma, susceptibility to | 2011-06-19 | no assertion criteria provided | literature only |