NM_003977.4(AIP):c.803A>G (p.Tyr268Cys) AND Hereditary cancer-predisposing syndrome

Clinical significance:Uncertain significance (Last evaluated: Aug 14, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_003977.4(AIP):c.803A>G (p.Tyr268Cys)]

NM_003977.4(AIP):c.803A>G (p.Tyr268Cys)

AIP:aryl hydrocarbon receptor interacting protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_003977.4(AIP):c.803A>G (p.Tyr268Cys)
  • NC_000011.10:g.67490803A>G
  • NG_008969.1:g.12770A>G
  • NM_001302959.1:c.626A>G
  • NM_001302960.2:c.795A>G
  • NM_003977.4:c.803A>GMANE SELECT
  • NP_001289888.1:p.Tyr209Cys
  • NP_001289889.1:p.Leu265=
  • NP_003968.3:p.Tyr268Cys
  • LRG_460t1:c.803A>G
  • LRG_460:g.12770A>G
  • NC_000011.9:g.67258274A>G
  • NM_003977.2:c.803A>G
Protein change:
dbSNP: rs267606577
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001302959.1:c.626A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003977.4:c.803A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001302960.2:c.795A>G - synonymous variant - [Sequence Ontology: SO:0001819]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001189601Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Aug 14, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas.

Tichomirowa MA, Barlier A, Daly AF, Jaffrain-Rea ML, Ronchi C, Yaneva M, Urban JD, Petrossians P, Elenkova A, Tabarin A, Desailloud R, Maiter D, Schürmeyer T, Cozzi R, Theodoropoulou M, Sievers C, Bernabeu I, Naves LA, Chabre O, Montañana CF, Hana V, Halaby G, et al.

Eur J Endocrinol. 2011 Oct;165(4):509-15. doi: 10.1530/EJE-11-0304. Epub 2011 Jul 13.

PubMed [citation]

Structure of the TPR domain of AIP: lack of client protein interaction with the C-terminal α-7 helix of the TPR domain of AIP is sufficient for pituitary adenoma predisposition.

Morgan RM, Hernández-Ramírez LC, Trivellin G, Zhou L, Roe SM, Korbonits M, Prodromou C.

PLoS One. 2012;7(12):e53339. doi: 10.1371/journal.pone.0053339. Epub 2012 Dec 31.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001189601.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)


The p.Y268C variant (also known as c.803A>G), located in coding exon 6 of the AIP gene, results from an A to G substitution at nucleotide position 803. The tyrosine at codon 268 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in individuals with apparent sporadic pituitary macroadenomas (Tichomirowa MA et al. Eur. J. Endocrinol., 2011 Oct;165:509-15; Beckers A et al. Endocr. Rev., 2013 Apr;34:239-77). This alteration is located in the functional significant tetratricopeptide repeat domain of the AIP protein, and a structural analysis suggests it may disrupt packing of the hydrophobic core (Morgan RM et al. PLoS ONE, 2012 Dec;7:e53339). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2021

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