ClinVar Miner

Submissions for variant NM_001365999.1(SZT2):c.1373G>A (p.Arg458Gln) (rs547358307)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482376 SCV000573119 uncertain significance not provided 2017-02-15 criteria provided, single submitter clinical testing The R458Q variant in the SZT2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This 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 R458Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R458Q as a variant of uncertain significance.
Invitae RCV000482376 SCV000951828 uncertain significance not provided 2019-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 458 of the SZT2 protein (p.Arg458Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs547358307, ExAC 0.02%). This variant has not been reported in the literature in individuals with SZT2-related disease. ClinVar contains an entry for this variant (Variation ID: 423418). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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