U.S. flag

An official website of the United States government

NM_000044.6(AR):c.2599G>A (p.Val867Met) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 11, 2020
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:
RCV001381188.9

Allele description [Variation Report for NM_000044.6(AR):c.2599G>A (p.Val867Met)]

NM_000044.6(AR):c.2599G>A (p.Val867Met)

Gene:
AR:androgen receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq12
Genomic location:
Preferred name:
NM_000044.6(AR):c.2599G>A (p.Val867Met)
HGVS:
  • NC_000023.11:g.67722976G>A
  • NG_009014.2:g.183945G>A
  • NM_000044.6:c.2599G>AMANE SELECT
  • NM_001011645.3:c.1003G>A
  • NP_000035.2:p.Val867Met
  • NP_001011645.1:p.Val335Met
  • LRG_1406t1:c.2599G>A
  • LRG_1406:g.183945G>A
  • LRG_1406p1:p.Val867Met
  • NC_000023.10:g.66942818G>A
  • NM_000044.3:c.2599G>A
  • NM_000044.4:c.2599G>A
  • P10275:p.Val867Met
Protein change:
V335M
Links:
UniProtKB: P10275#VAR_004730; OMIM: 313700.0005; OMIM: 313700.0017; dbSNP: rs137852564
NCBI 1000 Genomes Browser:
rs137852564
Molecular consequence:
  • NM_000044.6:c.2599G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001011645.3:c.1003G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Unknown function

Condition(s)

Name:
Androgen resistance syndrome (AIS)
Synonyms:
TESTICULAR FEMINIZATION SYNDROME; Androgen insensitivity syndrome; Androgen receptor deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019154; MedGen: C0039585; Orphanet: 99429; OMIM: 300068
Name:
Kennedy disease (SMAX1)
Synonyms:
SPINAL AND BULBAR MUSCULAR ATROPHY, X-LINKED 1; Bulbo-spinal atrophy X-linked; Kennedy spinal and bulbar muscular atrophy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010735; MedGen: C1839259; Orphanet: 481; OMIM: 313200

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001579481Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 11, 2020) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity.

Hornig NC, Ukat M, Schweikert HU, Hiort O, Werner R, Drop SL, Cools M, Hughes IA, Audi L, Ahmed SF, Demiri J, Rodens P, Worch L, Wehner G, Kulle AE, Dunstheimer D, Müller-Roßberg E, Reinehr T, Hadidi AT, Eckstein AK, van der Horst C, Seif C, et al.

J Clin Endocrinol Metab. 2016 Nov;101(11):4468-4477. Epub 2016 Sep 1.

PubMed [citation]
PMID:
27583472
PMCID:
PMC5095254

Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity.

Lubahn DB, Brown TR, Simental JA, Higgs HN, Migeon CJ, Wilson EM, French FS.

Proc Natl Acad Sci U S A. 1989 Dec;86(23):9534-8. Erratum in: Proc Natl Acad Sci U S A 1990 Jun;87(11):4411.

PubMed [citation]
PMID:
2594783
PMCID:
PMC298531
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001579481.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces valine with methionine at codon 867 of the AR protein (p.Val867Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant is located in the ligand binding domain of the androgen receptor(AR) protein and experimental evidence using genital fibroblast cultures shows this variant has reduced dihydrotestosterone(DHT)-dependent, AR-induced transcriptional activation (PMID: 27583472). This variant has been reported in individuals and families affected with partial androgen insensitivity syndrome (PMID: 2594783, 26806084, 26688387). This variant is also known as p.Val866Met. ClinVar contains an entry for this variant (Variation ID: 9806).

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

Last Updated: Sep 29, 2024