ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.694C>T (p.Arg232Cys)

gnomAD frequency: 0.00004  dbSNP: rs186526524
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179843 SCV000232158 uncertain significance not provided 2014-10-21 criteria provided, single submitter clinical testing
Invitae RCV000556160 SCV000652296 uncertain significance Usher syndrome type 3B 2024-01-31 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 232 of the HARS protein (p.Arg232Cys). This variant is present in population databases (rs186526524, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with HARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 198477). 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) performed at Invitae indicates that this missense variant is expected to disrupt HARS protein function with a positive predictive value of 80%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000179843 SCV001714148 uncertain significance not provided 2020-10-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002460958 SCV002755239 likely benign Inborn genetic diseases 2020-12-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.