Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000263998 | SCV000329852 | pathogenic | not provided | 2016-09-09 | criteria provided, single submitter | clinical testing | The N772H variant in the AR gene has been reported previously as N771H using alternate nomenclature in association with partial androgen insensitivity, and its presence is consistent with the diagnosis in this patient. This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N772H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. The N772H variant is located within the ligand binding domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a functional study has shown that this variant (reported as N771H using alternate nomenclature) significantly decreased the dose-response of dihydrotestosterone-induced transactivation activity (Cai et al., 2012). Missense variants in nearby residues (P767A, P767S, D768Y, D768V, D768E, L769V, L769M, L769P, E773G, E773A, Y774H, Y774C, R775C, R775H, R775L) have been reported in the Human Gene Mutation Database in association with Androgen insensitivity syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we consider this variant to be pathogenic. |
Genome |
RCV001175283 | SCV001338893 | not provided | Partial androgen insensitivity syndrome | no assertion provided | phenotyping only | Variant interpretted as Pathogenic and reported on 09-13-2016 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |