Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000815685 | SCV000956149 | uncertain significance | Androgen resistance syndrome; Kennedy disease | 2018-10-13 | criteria provided, single submitter | clinical testing | This variant disrupts the p.His690 amino acid residue in AR. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 12213902), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease.  This residue has also been reported as p.His689. 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AR-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with asparagine at codon 690 of the AR protein (p.His690Asn). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and asparagine. |