NM_000044.6(AR):c.2128G>A (p.Glu710Lys) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 16, 2019
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:: RCV001208881.7

Allele description

NM_000044.6(AR):c.2128G>A (p.Glu710Lys)

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.2128G>A (p.Glu710Lys)

HGVS:

NC_000023.11:g.67711644G>A
NG_009014.2:g.172613G>A
NM_000044.6:c.2128G>AMANE SELECT
NM_001011645.3:c.532G>A
NP_000035.2:p.Glu710Lys
NP_001011645.1:p.Glu178Lys
LRG_1406t1:c.2128G>A
LRG_1406:g.172613G>A
LRG_1406p1:p.Glu710Lys
NC_000023.10:g.66931486G>A
NM_000044.3:c.2128G>A

Protein change:

E178K

Links:

dbSNP: rs2076094436

NCBI 1000 Genomes Browser:

rs2076094436

Molecular consequence:

NM_000044.6:c.2128G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001011645.3:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001380290	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 16, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12068007, 9576916, 16373394, 24790346, 25433660, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001380290

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 16, 2019)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations in the helix 3 region of the androgen receptor abrogate ARA70 promotion of 17beta-estradiol-induced androgen receptor transactivation.

Thin TH, Kim E, Yeh S, Sampson ER, Chen YT, Collins LL, Basavappa R, Chang C.

J Biol Chem. 2002 Sep 27;277(39):36499-508. Epub 2002 Jun 14.

PubMed [citation]

PMID:: 12068007

From estrogen to androgen receptor: a new pathway for sex hormones in prostate.

Yeh S, Miyamoto H, Shima H, Chang C.

Proc Natl Acad Sci U S A. 1998 May 12;95(10):5527-32.

PubMed [citation]

PMID:: 9576916
PMCID:: PMC20411

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001380290.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect AR protein function (PMID: 9576916, 12068007, 16373394). This variant has been observed in individuals affected with partial or complete androgen insensitivity syndrome (PMID: 9576916, 16373394, 24790346, 25433660). It is also known as p.Glu709Lys and p.Glu708Lys in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 710 of the AR protein (p.Glu710Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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

Last Updated: Mar 5, 2024

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