Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815871 | SCV000956347 | likely pathogenic | Androgen resistance syndrome; Kennedy disease | 2018-08-21 | criteria provided, single submitter | clinical testing | This variant has been observed in several individuals affected with androgen insensitivity syndrome (PMID: 8723113, 27899157, 29051026). This variant has also been reported as p.Val746Met. This sequence change replaces valine with methionine at codon 747 of the AR protein (p.Val747Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). 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"). 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. |