ClinVar Miner

Submissions for variant NM_000044.6(AR):c.2599G>A (p.Val867Met) (rs137852564)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000010480 SCV000629595 pathogenic Androgen resistance syndrome 2017-02-27 criteria provided, single submitter clinical testing 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). 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). 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). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763628 SCV000894496 pathogenic Androgen resistance syndrome; Bulbo-spinal atrophy X-linked; Partial androgen insensitivity syndrome; Hypospadias 1, X-linked; Malignant tumor of prostate 2018-10-31 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000010480 SCV001334246 pathogenic Androgen resistance syndrome 2020-02-18 criteria provided, single submitter clinical testing A homozygous missense variation in exon 7 of the AR gene that results in amino acid substitution of methionine for valine at codon 867 was detected. The observed variant c.2599G>A has not been reported in the 1000 genomes and ExAC databases. The variant lies in the ligand-binding domain of nuclear hormone receptor domain of the AR protein and has previously been reported as p.Val866Met in patients affected with androgen insensitivity (Lubahn et al. 1989). The in silico prediction of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.
OMIM RCV000010480 SCV000030706 pathogenic Androgen resistance syndrome 1989-12-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000010480 SCV000692172 pathogenic Androgen resistance syndrome 2016-08-05 no assertion criteria provided clinical testing

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