NM_003977.4(AIP):c.174G>C (p.Lys58Asn) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001038333.7

Allele description [Variation Report for NM_003977.4(AIP):c.174G>C (p.Lys58Asn)]

NM_003977.4(AIP):c.174G>C (p.Lys58Asn)

Genes:

LOC130006206:ATAC-STARR-seq lymphoblastoid active region 5107 [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.174G>C (p.Lys58Asn)

HGVS:

NC_000011.10:g.67487080G>C
NG_008969.1:g.9047G>C
NM_001302959.2:c.-4G>C
NM_001302960.2:c.174G>C
NM_003977.4:c.174G>CMANE SELECT
NP_001289889.1:p.Lys58Asn
NP_003968.3:p.Lys58Asn
LRG_460t1:c.174G>C
LRG_460:g.9047G>C
NC_000011.9:g.67254551G>C
NM_003977.2:c.174G>C
NM_003977.3:c.174G>C

Protein change:

K58N

Links:

dbSNP: rs267606539

NCBI 1000 Genomes Browser:

rs267606539

Molecular consequence:

NM_001302959.2:c.-4G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001302960.2:c.174G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003977.4:c.174G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201799	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21753072, 22319033, 23321498, 28492532
SCV003933386	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 15, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001201799

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2024)

germline

clinical testing

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

SCV003933386

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 15, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, 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]

PMID:: 21753072

Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients.

Cazabat L, Bouligand J, Salenave S, Bernier M, Gaillard S, Parker F, Young J, Guiochon-Mantel A, Chanson P.

J Clin Endocrinol Metab. 2012 Apr;97(4):E663-70. doi: 10.1210/jc.2011-2291. Epub 2012 Feb 8.

PubMed [citation]

PMID:: 22319033

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001201799.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 58 of the AIP protein (p.Lys58Asn). This variant is present in population databases (rs267606539, gnomAD 0.002%). This missense change has been observed in individual(s) with pituitary adenoma (PMID: 21753072, 22319033, 23321498). ClinVar contains an entry for this variant (Variation ID: 41166). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AIP protein function with a negative predictive value of 80%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003933386.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with isolated sporadic pituitary adenomas (Tichomirowa et al., 2011; Cazabat et al., 2012); This variant is associated with the following publications: (PMID: 21753072, 23371967, 22319033, 23321498, 31351448)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine