Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000640474 | SCV000762066 | pathogenic | Androgen resistance syndrome; Kennedy disease | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 841 of the AR protein (p.Arg841Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with partial androgen insensitivity syndrome (PMID: 1430233, 8040309, 8824883, 11788673, 15925895, 20011049). It has also been observed to segregate with disease in related individuals. This variant is also known as R838C, R839C, and R840C. ClinVar contains an entry for this variant (Variation ID: 9830). 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. Experimental studies have shown that this missense change affects AR function (PMID: 1430233, 8040309, 9768671, 16083860, 20011049). For these reasons, this variant has been classified as Pathogenic. |
Clinical Genetics and Genomics, |
RCV001269809 | SCV001450082 | pathogenic | not provided | 2020-02-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001269809 | SCV003921641 | pathogenic | not provided | 2022-10-25 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate abnormal regulation of the NC-TDI interaction and reduced transcriptional activity (Szafran et al., 2009); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 29582157, 33516834, 16083860, 34755921, 30316867, 7929841, 33750429, 1430233, 20011049, 9768671, 8824883, 8040309, 32345305, 15925895, 11788673) |
OMIM | RCV000010504 | SCV000030730 | pathogenic | Partial androgen insensitivity syndrome | 1994-08-01 | no assertion criteria provided | literature only | |
OMIM | RCV000010529 | SCV000030755 | pathogenic | Androgen resistance syndrome | 2002-01-01 | no assertion criteria provided | literature only | |
Clinical Molecular Genetics Laboratory, |
RCV000010529 | SCV000692166 | pathogenic | Androgen resistance syndrome | 2011-01-26 | no assertion criteria provided | clinical testing |