Submissions for variant NM_014159.7(SETD2):c.2849G>A (p.Arg950His)

gnomAD frequency: 0.00004  dbSNP: rs149265978

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001345358	SCV001539469	uncertain significance	Luscan-Lumish syndrome	2021-08-26	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with histidine at codon 950 of the SETD2 protein (p.Arg950His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs149265978, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with SETD2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Revvity Omics, Revvity	RCV003136009	SCV003819427	uncertain significance	not provided	2020-04-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003136009	SCV004185057	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	SETD2: BP4