Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000640476 | SCV000762068 | likely pathogenic | Androgen resistance syndrome; Kennedy disease | 2021-09-01 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly569 amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in individuals with AR-related conditions (PMID: 20150575, 27583472, 27849622), 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 C15"). ClinVar contains an entry for this variant (Variation ID: 533379). This missense change has been observed in individuals with complete androgen insensitivity syndrome (PMID: 7910529, 28624954; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with tryptophan at codon 569 of the AR protein (p.Gly569Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. |