Submissions for variant NM_000044.6(AR):c.2507T>G (p.Ile836Ser)

dbSNP: rs2076141961

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568712	SCV003315287	uncertain significance	Androgen resistance syndrome; Kennedy disease	2022-09-21	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 836 of the AR protein (p.Ile836Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with complete androgen insensitivity syndrome (PMID: 33505695). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 974911). 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. 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.
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine	RCV001251210	SCV001371843	pathogenic	Androgen resistance syndrome		no assertion criteria provided	research
Human Developmental Genetics, Institut Pasteur	RCV001251210	SCV001787097	pathogenic	Androgen resistance syndrome	2021-08-17	no assertion criteria provided	research