NM_000044.6(AR):c.2231G>T (p.Gly744Val) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 21, 2021
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:: RCV001851781.5

Allele description [Variation Report for NM_000044.6(AR):c.2231G>T (p.Gly744Val)]

NM_000044.6(AR):c.2231G>T (p.Gly744Val)

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.2231G>T (p.Gly744Val)

Other names:

G743V

HGVS:

NC_000023.11:g.67717535G>T
NG_009014.2:g.178504G>T
NM_000044.6:c.2231G>TMANE SELECT
NM_001011645.3:c.635G>T
NP_000035.2:p.Gly744Val
NP_001011645.1:p.Gly212Val
LRG_1406t1:c.2231G>T
LRG_1406:g.178504G>T
LRG_1406p1:p.Gly744Val
NC_000023.10:g.66937377G>T
P10275:p.Gly744Val

Protein change:

G212V; GLY743VAL

Links:

UniProtKB: P10275#VAR_004699; OMIM: 313700.0056; dbSNP: rs137852600

NCBI 1000 Genomes Browser:

rs137852600

Molecular consequence:

NM_000044.6:c.2231G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001011645.3:c.635G>T - 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
SCV002242613	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 21, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8096390, 8325932, 9768671, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002242613

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 21, 2021)

germline

clinical testing

PubMed (4)
[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

Complete androgen insensitivity syndrome associated with a de novo mutation of the androgen receptor gene detected by single strand conformation polymorphism.

Lobaccaro JM, Lumbroso S, Berta P, Chaussain JL, Sultan C.

J Steroid Biochem Mol Biol. 1993 Mar;44(3):211-6.

PubMed [citation]

PMID:: 8096390

A single amino acid substitution (gly743 --> val) in the steroid-binding domain of the human androgen receptor leads to Reifenstein syndrome.

Nakao R, Yanase T, Sakai Y, Haji M, Nawata H.

J Clin Endocrinol Metab. 1993 Jul;77(1):103-7.

PubMed [citation]

PMID:: 8325932

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002242613.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects AR protein function (PMID: 8325932, 9768671). This variant has been observed in individual(s) with androgen insensitivity syndrome (PMID: 8096390, 8325932, 9768671). In at least one individual the variant was observed to be de novo. This variant is also known as Gly743Val. ClinVar contains an entry for this variant (Variation ID: 9857). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 744 of the AR protein (p.Gly744Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine.

#	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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