ClinVar Miner

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

gnomAD frequency: 0.00005  dbSNP: rs777992018
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
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 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1459 of the SETD2 protein (p.Arg1459Gln). This variant is present in population databases (rs777992018, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with SETD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 373451). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SETD2 protein function. 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 Autism; Intellectual disability 2020-01-21 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001064806 SCV002555508 uncertain significance Luscan-Lumish syndrome 2022-03-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.