ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.494G>A (p.Arg165His)

gnomAD frequency: 0.00004  dbSNP: rs373522589
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001318384 SCV001509083 uncertain significance Usher syndrome type 3B 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 165 of the HARS protein (p.Arg165His). This variant is present in population databases (rs373522589, gnomAD 0.007%). 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: 1019008). 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 not expected to disrupt HARS protein function with a negative 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.
GeneDx RCV002462929 SCV002756606 uncertain significance not provided 2022-05-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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