ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.797G>A (p.Arg266His) (rs765223763)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757351 SCV000885541 uncertain significance not provided 2017-12-12 criteria provided, single submitter clinical testing The p.Arg266His variant (rs765223763) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Genome Aggregation Database (gnomAD). The arginine at position 266 is weakly conserved considering 12 species (Alamut v2.10) and computational analyses of the effects of the p.Arg266His variant on protein structure and function provide conflicting results (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Arg266His variant with certainty.
Invitae RCV001047038 SCV001210970 uncertain significance Usher syndrome, type 3B 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 266 of the HARS protein (p.Arg266His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs765223763, ExAC 0.001%). This variant has not been reported in the literature in individuals with HARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 618673). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.