ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.52G>A (p.Val18Met) (rs774632798)

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
Invitae RCV000524753 SCV000652294 uncertain significance Usher syndrome, type 3B 2019-06-11 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 18 of the HARS protein (p.Val18Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs774632798, ExAC 0.008%). This variant has not been reported in the literature in individuals with a HARS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on HARS function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001086 SCV001158221 uncertain significance not specified 2019-03-04 criteria provided, single submitter clinical testing The HARS c.52G>A; p.Val18Met variant (rs774632798), to our knowledge, is not described in the medical literature but contains an entry in ClinVar (Variation ID: 472993). It is observed in the general population at an overall frequency of 0.005% (14/278134 alleles) in the Genome Aggregation Database. The valine at codon 18 is moderately conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty.

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.