ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.1402G>A (p.Glu468Lys)

gnomAD frequency: 0.00014  dbSNP: rs199615869
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000650149 SCV000771986 uncertain significance Usher syndrome type 3B 2024-11-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 468 of the HARS protein (p.Glu468Lys). This variant is present in population databases (rs199615869, gnomAD 0.02%). 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: 540202). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
CeGaT Center for Human Genetics Tuebingen RCV000998447 SCV001154530 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000998447 SCV001805634 uncertain significance not provided 2024-03-18 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
Ambry Genetics RCV004025793 SCV002755234 likely benign not specified 2021-09-01 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000998447 SCV005411877 uncertain significance not provided 2023-07-05 criteria provided, single submitter clinical testing

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