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NM_000044.6(AR):c.1859G>A (p.Cys620Tyr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 25, 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:
RCV001060093.8

Allele description [Variation Report for NM_000044.6(AR):c.1859G>A (p.Cys620Tyr)]

NM_000044.6(AR):c.1859G>A (p.Cys620Tyr)

Gene:
AR:androgen receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq12
Genomic location:
Preferred name:
NM_000044.6(AR):c.1859G>A (p.Cys620Tyr)
HGVS:
  • NC_000023.11:g.67686100G>A
  • NG_009014.2:g.147069G>A
  • NM_000044.6:c.1859G>AMANE SELECT
  • NM_001011645.3:c.263G>A
  • NM_001348061.1:c.1859G>A
  • NM_001348063.1:c.1859G>A
  • NM_001348064.1:c.*57G>A
  • NP_000035.2:p.Cys620Tyr
  • NP_001011645.1:p.Cys88Tyr
  • NP_001334990.1:p.Cys620Tyr
  • NP_001334992.1:p.Cys620Tyr
  • LRG_1406t1:c.1859G>A
  • LRG_1406:g.147069G>A
  • LRG_1406p1:p.Cys620Tyr
  • NC_000023.10:g.66905942G>A
  • NM_000044.3:c.1859G>A
Protein change:
C620Y
Links:
dbSNP: rs1312745277
NCBI 1000 Genomes Browser:
rs1312745277
Molecular consequence:
  • NM_001348064.1:c.*57G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000044.6:c.1859G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001011645.3:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348061.1:c.1859G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001348063.1:c.1859G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001224755Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 25, 2022) 		germlineclinical testing

PubMed (3)
[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

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

Audi L, Fernández-Cancio M, Carrascosa A, Andaluz P, Torán N, Piró C, Vilaró E, Vicens-Calvet E, Gussinyé M, Albisu MA, Yeste D, Clemente M, Hernández de la Calle I, Del Campo M, Vendrell T, Blanco A, Martínez-Mora J, Granada ML, Salinas I, Forn J, Calaf J, Angerri O, et al.

J Clin Endocrinol Metab. 2010 Apr;95(4):1876-88. doi: 10.1210/jc.2009-2146. Epub 2010 Feb 11.

PubMed [citation]
PMID:
20150575

Somatic mosaicism of androgen receptor gene in an androgen insensitivity syndrome patient conceived through assisted reproduction technique.

Wang H, Zhu H, Wang N, Cheng T, Han B, Zhao S, Song H, Cheng K, Liu Y, Qiao J.

Mol Genet Genomic Med. 2019 Oct;7(10):e00906. doi: 10.1002/mgg3.906. Epub 2019 Aug 20.

PubMed [citation]
PMID:
31429517
PMCID:
PMC6785456
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224755.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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. This variant disrupts the p.Cys620 amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in individuals with AR-related conditions (PMID: 20150575, 31429517), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 854942). This missense change has been observed in individual(s) with androgen insensitivity syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 620 of the AR protein (p.Cys620Tyr).

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

Last Updated: Sep 29, 2024