ClinVar Miner

Submissions for variant NM_000044.6(AR):c.2522G>A (p.Arg841His) (rs9332969)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814875 SCV000955308 pathogenic Androgen resistance syndrome; Bulbo-spinal atrophy X-linked 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 841 of the AR protein (p.Arg841His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with androgen insensitivity syndome (PMID: 1430233, 28624954, 8040309) and segregated with disease in several families (PMID: 16450583, 28186600, 25241384, 8040309, 27267075). This variant is also known as p.R838H, p.R839H, and p.R840H. ClinVar contains an entry for this variant (Variation ID: 9829). Experimental studies have shown that this missense change displayed negative or abnormal hormone binding in COS-1 cells (PMID: 8040309) and in genital skin fibroblasts  (PMID: 1430233). This variant disrupts the p.Arg941 amino acid residue in AR. Other variants that disrupt this residue have been observed in affected individuals (PMID: 1430233, 8040309, 20011049, 8824883, 15925895, 11788673), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000010503 SCV000030729 pathogenic Partial androgen insensitivity syndrome 1994-08-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000582333 SCV000692167 pathogenic Androgen resistance syndrome 2007-11-30 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.