ClinVar Miner

Submissions for variant NM_005051.3(QARS1):c.1559C>T (p.Thr520Met)

gnomAD frequency: 0.00006  dbSNP: rs764216449
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438114 SCV000535437 uncertain significance not provided 2016-12-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the QARS gene. The T520M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T520M variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T520M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001238962 SCV001411802 uncertain significance Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome 2022-07-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 520 of the QARS protein (p.Thr520Met). This variant is present in population databases (rs764216449, gnomAD 0.006%). 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: 392210). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

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