ClinVar Miner

Submissions for variant NM_002382.5(MAX):c.223C>T (p.Arg75Ter) (rs387906650)

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Total submissions: 3
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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

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