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

gnomAD frequency: 0.00005  dbSNP: rs777992018

Total submissions: 7

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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064806	SCV001229727	benign	Luscan-Lumish syndrome	2024-11-05	criteria provided, single submitter	clinical testing
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	RCV001064806	SCV001432850	uncertain significance	Luscan-Lumish syndrome	2022-01-21	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
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004696908	SCV005198214	uncertain significance	not provided	2023-03-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004965448	SCV005495688	likely benign	Inborn genetic diseases	2024-11-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.