Submissions for variant NM_003977.4(AIP):c.783C>G (p.Tyr261Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002412154	SCV002671385	pathogenic	Hereditary cancer-predisposing syndrome	2020-09-09	criteria provided, single submitter	clinical testing	The p.Y261* pathogenic mutation (also known as c.783C>G), located in coding exon 5 of the AIP gene, results from a C to G substitution at nucleotide position 783. This changes the amino acid from a tyrosine to a stop codon within coding exon 5. This variant was first reported in the literature in an individual with sporadic pituitary adenoma who presented with gigantism at age 17 (Cazabat L et al. J. Clin. Endocrinol. Metab., 2012 Apr;97:E663-70). Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of AIP, is not expected to trigger nonsense-mediated mRNA decay, and removes the last 70 amino acids of the protein. While the exact functional impact of these removed amino acids is unknown at this time, the final carboxy-terminal amino acids are presumed necessary for interactions of AIP with heat shock protein 90 (hsp90) and the aryl hydrocarbon receptor (AhR) (Petrulis JR et al. Chem. Biol. Interact., 2002 Sep;141:25-40; Daly AF et al. J. Clin. Endocrinol. Metab., 2007 May;92:1891-6). As such, this alteration is interpreted as a disease-causing mutation.