ClinVar Miner

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

gnomAD frequency: 0.00006  dbSNP: rs774632798
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000524753 SCV000652294 uncertain significance Usher syndrome type 3B 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 18 of the HARS protein (p.Val18Met). This variant is present in population databases (rs774632798, gnomAD 0.009%). 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: 472993). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
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.
PreventionGenetics, part of Exact Sciences RCV003409814 SCV004115369 uncertain significance HARS1-related condition 2023-02-20 criteria provided, single submitter clinical testing The HARS1 c.52G>A variant is predicted to result in the amino acid substitution p.Val18Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0086% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-140070838-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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