Total submissions: 3
| 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, |
RCV000582333 | SCV000692167 | pathogenic | Androgen resistance syndrome | 2007-11-30 | no assertion criteria provided | clinical testing |