ClinVar Miner

Submissions for variant NM_005051.3(QARS1):c.1570C>T (p.Arg524Trp)

gnomAD frequency: 0.00002  dbSNP: rs774980346
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000415807 SCV000493619 likely pathogenic not provided 2016-07-01 criteria provided, single submitter clinical testing
Invitae RCV000415807 SCV002284272 uncertain significance not provided 2021-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 524 of the QARS protein (p.Arg524Trp). This variant is present in population databases (rs774980346, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with QARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 374729). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003488584 SCV004241624 uncertain significance not specified 2023-12-22 criteria provided, single submitter clinical testing Variant summary: QARS1 c.1570C>T (p.Arg524Trp) results in a non-conservative amino acid change located in the Glutamyl/glutaminyl-tRNA synthetase, class Ib, catalytic domain (IPR020058) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.1e-05 in 282846 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1570C>T in individuals affected with Diffuse Cerebral And Cerebellar Atrophy-Intractable Seizures-Progressive Microcephaly Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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