NM_003977.4(AIP):c.166C>T (p.Arg56Cys) AND not provided

Clinical significance:Uncertain significance (Last evaluated: May 12, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001326205.2

Allele description [Variation Report for NM_003977.4(AIP):c.166C>T (p.Arg56Cys)]

NM_003977.4(AIP):c.166C>T (p.Arg56Cys)

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.166C>T (p.Arg56Cys)
HGVS:
  • NC_000011.10:g.67487072C>T
  • NG_008969.1:g.9039C>T
  • NM_001302959.2:c.-12C>T
  • NM_001302960.2:c.166C>T
  • NM_003977.4:c.166C>TMANE SELECT
  • NP_001289889.1:p.Arg56Cys
  • NP_003968.3:p.Arg56Cys
  • LRG_460t1:c.166C>T
  • LRG_460:g.9039C>T
  • NC_000011.9:g.67254543C>T
  • NM_003977.2:c.166C>T
Protein change:
R56C
Links:
Molecular consequence:
  • NM_001302959.2:c.-12C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001302960.2:c.166C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003977.4:c.166C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001517226Invitaecriteria provided, single submitter
Uncertain significance
(May 12, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002005065GeneDxcriteria provided, single submitter
Uncertain significance
(Mar 26, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, Sch├╝rmeyer T, Cozzi R, Theodoropoulou M, Sievers C, Bernabeu I, Naves LA, Chabre O, Monta├▒ana 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]
PMID:
21753072

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001517226.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with cysteine at codon 56 of the AIP protein (p.Arg56Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs267606538, ExAC 0.003%). This variant has been observed in individual(s) with pituitary macroadenoma (PMID: 21753072). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV002005065.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with prolactinoma (Tichomirowa 2011); This variant is associated with the following publications: (PMID: 21753072, 23371967)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 5, 2021

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