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NM_003977.4(AIP):c.911G>A (p.Arg304Gln) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 25, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000439236.6

Allele description [Variation Report for NM_003977.4(AIP):c.911G>A (p.Arg304Gln)]

NM_003977.4(AIP):c.911G>A (p.Arg304Gln)

Gene:
AIP:aryl hydrocarbon receptor interacting protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.2
Genomic location:
Preferred name:
NM_003977.4(AIP):c.911G>A (p.Arg304Gln)
HGVS:
  • NC_000011.10:g.67490911G>A
  • NG_008969.1:g.12878G>A
  • NM_001302959.2:c.734G>A
  • NM_001302960.2:c.*51G>A
  • NM_003977.4:c.911G>AMANE SELECT
  • NP_001289888.1:p.Arg245Gln
  • NP_003968.3:p.Arg304Gln
  • LRG_460t1:c.911G>A
  • LRG_460:g.12878G>A
  • NC_000011.9:g.67258382G>A
  • NM_003977.2:c.911G>A
  • NM_003977.3:c.911G>A
Protein change:
R245Q; ARG304GLN
Links:
OMIM: 605555.0008; dbSNP: rs104894190
NCBI 1000 Genomes Browser:
rs104894190
Molecular consequence:
  • NM_001302960.2:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001302959.2:c.734G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003977.4:c.911G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000538256Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Sep 25, 2018) 		germlineclinical testing

PubMed (16)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia.

Occhi G, Trivellin G, Ceccato F, De Lazzari P, Giorgi G, Demattè S, Grimaldi F, Castello R, Davì MV, Arnaldi G, Salviati L, Opocher G, Mantero F, Scaroni C.

Eur J Endocrinol. 2010 Sep;163(3):369-76. doi: 10.1530/EJE-10-0327. Epub 2010 Jun 7.

PubMed [citation]
PMID:
20530095

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.

Georgitsi M, Raitila A, Karhu A, Tuppurainen K, Mäkinen MJ, Vierimaa O, Paschke R, Saeger W, van der Luijt RB, Sane T, Robledo M, De Menis E, Weil RJ, Wasik A, Zielinski G, Lucewicz O, Lubinski J, Launonen V, Vahteristo P, Aaltonen LA.

Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4101-5. Epub 2007 Feb 28.

PubMed [citation]
PMID:
17360484
PMCID:
PMC1820715
See all PubMed Citations (16)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000538256.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (16)

Description

The p.Arg304Gln variant in AIP has been reported in >10 individuals with pituita ry adenoma and segregated with disease in two affected members across two famili es (Georgitsi 2007, Igreja 2010, Occhi 2010, Tichomirowa 2011, Cazabat 2012, Cun y 2013, Pardi 2013, Preda 2014, Schofl 2014, Arajuo 2017). This variant has also been identified in multiple individuals without pituitary lesions (Tichomirowa 2011, Freudenberg-Hua 2014, Pardi 2013) and in 2.07% (208/10074) of Ashkenazi Je wish chromosomes, including 2 homozygous individuals, by gnomAD (http://gnomad.b roadinstitute.org). However, this frequency does not rule out a pathogenic role due to the prevalence of pituitary adenoma in the general population (~11% on au topsy; Molitch 2008) and the reduced penetrance of pituitary adenoma in individu als carrying pathogenic AIP variants (15-30%; Korbonits 2018). In vitro function al studies suggest that the p.Arg304Gln variant does not have a strong impact on protein function (Georgitisi 2007, Igreja 2010, Morgan 2012); however these typ es of assays may not accurately represent biological function. Computational pre diction tools and conservation analysis do not provide strong support for or aga inst an impact to the protein. Finally, this variant is present in ClinVar with conflicting interpretations of pathogenicity (Variation ID# 4893). In summary, t he clinical significance of the p.Arg304Gln variant is uncertain. ACMG/AMP Crit eria applied: PS4_Moderate, BS3_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Sep 29, 2024