NM_000044.6(AR):c.2191_2199del (p.Val731_Asp733del) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 17, 2022
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:: RCV002851524.3

Allele description [Variation Report for NM_000044.6(AR):c.2191_2199del (p.Val731_Asp733del)]

NM_000044.6(AR):c.2191_2199del (p.Val731_Asp733del)

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.2191_2199del (p.Val731_Asp733del)

HGVS:

NC_000023.11:g.67717495_67717503del
NG_009014.2:g.178464_178472del
NM_000044.6:c.2191_2199delMANE SELECT
NM_001011645.3:c.595_603del
NP_000035.2:p.Val731_Asp733del
NP_001011645.1:p.Val199_Asp201del
LRG_1406t1:c.2191_2199del
LRG_1406:g.178464_178472del
LRG_1406p1:p.Val731_Asp733del
NC_000023.10:g.66937335_66937343del
NC_000023.10:g.66937337_66937345del

Molecular consequence:

NM_000044.6:c.2191_2199del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001011645.3:c.595_603del - inframe_deletion - [Sequence Ontology: SO:0001822]

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003219976	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10425033, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003219976

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 17, 2022)

germline

clinical testing

PubMed (2)
[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

Update of the androgen receptor gene mutations database.

Gottlieb B, Beitel LK, Lumbroso R, Pinsky L, Trifiro M.

Hum Mutat. 1999;14(2):103-14.

PubMed [citation]

PMID:: 10425033

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003219976.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.2191_2199del, results in the deletion of 3 amino acid(s) of the AR protein (p.Val731_Asp733del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AR-related conditions. This variant disrupts a region of the AR protein in which other variant(s) (p.Asp733Asn) have been determined to be pathogenic (PMID: 10425033). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine