Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001058673 | SCV001223260 | uncertain significance | Androgen resistance syndrome; Kennedy disease | 2019-11-26 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.Ala242 (also reported as p.Ala240) amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in individuals with AR-related conditions (PMID: 21962961), 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 alanine with valine at codon 242 of the AR protein (p.Ala242Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. |