Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000814876 | SCV000955309 | pathogenic | Androgen resistance syndrome; Kennedy disease | 2023-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 843 of the AR protein (p.Ile843Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with androgen insensitivity syndrome (PMID: 8723113, 9039340, 22334387). This variant is also known as 842Ile-Thr. ClinVar contains an entry for this variant (Variation ID: 658124). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AR protein function. This variant disrupts the p.Ile843 amino acid residue in AR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11788645). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Human Developmental Genetics, |
RCV001568311 | SCV001787100 | pathogenic | Androgen resistance syndrome | 2021-08-17 | no assertion criteria provided | research |