Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000528841 | SCV000629594 | pathogenic | Androgen resistance syndrome; Kennedy disease | 2023-09-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects AR function (PMID: 2082179, 7633398, 10458483). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AR protein function. ClinVar contains an entry for this variant (Variation ID: 458366). This variant is also known as p.Arg830Gln and p.Arg831Gln. This missense change has been observed in individuals with androgen receptor insensitivity (PMID: 2082179, 10458483, 10834333, 20150575, 26778393). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 832 of the AR protein (p.Arg832Gln). |
| Ce |
RCV001200502 | SCV001371481 | pathogenic | not provided | 2020-06-01 | criteria provided, single submitter | clinical testing | |
| Clinical Genetics and Genomics, |
RCV001200502 | SCV001450281 | pathogenic | not provided | 2015-06-26 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002272280 | SCV002557532 | pathogenic | Androgen resistance syndrome | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with androgen insensitivity (MIM#300068), androgen insensitivity, partial, with or without breast cancer (MIM#312300), hypospadias 1, X-linked (MIM#300633), or spinal and bulbar muscular atrophy of Kennedy (MIM#313200). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0253 - This variant is hemizygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (0 heterozygotes, 0 homozygotes, 1 hemizygote). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ligand binding domain of the nuclear receptor androgen receptor (NCBI conserved domains). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported several times as pathogenic, and observed in hemizygous individuals with complete androgen insensitivity syndrome or aplasia of the uterus (ClinVar, DECIPHER, PMID: 30815925, PMID: 26778393, PMID: 2082179). (SP) 1001 - This variant has strong functional evidence supporting abnormal protein function. Genital fibroblasts from an affected individual were shown to abolish ligand binding ability (PMID: 2082179). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |