Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039615 | SCV001203152 | uncertain significance | Androgen resistance syndrome; Kennedy disease | 2019-03-22 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro683 (reported as p.Pro682) amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in individuals with AR-related conditions (PMID: 11587068, 15925895), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 683 of the AR protein (p.Pro683Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| 3billion | RCV001809960 | SCV002058324 | likely pathogenic | Partial androgen insensitivity syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | A different missense change at the same codon has been reported to be associated with AR related disorder (PMID:11587068,15925895, PM5_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant is located in a well-established functional domain or exonic hotspot, where pathogenic variants have frequently reported (PM1_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |