ClinVar Miner

Submissions for variant NM_001365999.1(SZT2):c.6724C>T (p.Arg2242Trp) (rs765848129)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493018 SCV000582428 likely pathogenic not provided 2017-08-21 criteria provided, single submitter clinical testing The R2185W variant in the SZT2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R2185W variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R2185W 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. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The R2185W variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded
Invitae RCV000493018 SCV001567213 uncertain significance not provided 2020-07-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 2185 of the SZT2 protein (p.Arg2185Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs765848129, ExAC 0.001%). This variant has been observed in individual(s) with SZT2-related conditions (PMID: 30560016, 30818181). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 429775). 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 C1). 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. 5
Institute for Biomedicine,Eurac Research RCV000664408 SCV000786628 likely pathogenic Early infantile epileptic encephalopathy 18 2018-07-16 no assertion criteria provided research This variant and NM_015284.3:c.498G>T (also submitted to ClinVar) were observed in a compound-heterozygous state in two affected brothers. The mother was unaffected and carried NM_015284.3:c.498G>T but not this variant, the father and another brother were unaffected and carried this variant but not NM_015284.3:c.498G>T.
OMIM RCV000664408 SCV001481163 pathogenic Early infantile epileptic encephalopathy 18 2021-02-19 no assertion criteria provided literature only

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