Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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- |
RCV001064806 | SCV002555508 | uncertain significance | Luscan-Lumish syndrome | 2022-03-15 | criteria provided, single submitter | clinical testing |