ClinVar Miner

Submissions for variant NM_014159.7(SETD2):c.4376G>A (p.Arg1459Gln) (rs777992018)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414404 SCV000492043 uncertain significance not specified 2016-11-29 criteria provided, single submitter clinical testing The R1459Q variant in the SETD2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1459Q 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 R1459Q 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 where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1459Q as a variant of uncertain significance.
Invitae RCV001064806 SCV001229727 uncertain significance Luscan-lumish syndrome 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1459 of the SETD2 protein (p.Arg1459Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs777992018, ExAC 0.005%). This variant has not been reported in the literature in individuals with SETD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373451). 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: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001064806 SCV001366644 uncertain significance Luscan-lumish syndrome 2019-04-25 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
New York Genome Center RCV001256063 SCV001432850 uncertain significance Autistic disorder of childhood onset; Intellectual disability 2020-01-21 criteria provided, single submitter clinical testing

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