Submissions for variant NM_002241.5(KCNJ10):c.53G>A (p.Arg18Gln)

gnomAD frequency: 0.01096  dbSNP: rs115466046

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000710154	SCV000169917	benign	not provided	2018-11-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27535533, 24794859, 21458570, 27884173, 27677466)
Eurofins Ntd Llc (ga)	RCV000117319	SCV000202876	benign	not specified	2014-03-18	criteria provided, single submitter	clinical testing
Invitae	RCV000234164	SCV000287322	benign	EAST syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000117319	SCV000297116	benign	not specified	2015-08-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000117319	SCV000308777	likely benign	not specified		criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000710154	SCV000613860	likely benign	not provided	2019-05-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312144	SCV000846149	benign	Inborn genetic diseases	2017-03-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina	RCV000234164	SCV001254026	uncertain significance	EAST syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258301	SCV001435248	benign	Autism; Seizure; Intellectual disability		criteria provided, single submitter	research	The heterozygous p.Arg18Gln variant in KCNJ10 has been identified in 2 individuals with autism, seizures, and intellectual disability and segregated with disease in 2 relatives from 1 family (PMID: 21458570). This variant has also been identified in >1% of European (non-Finnish) chromosomes and 11 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Arg18Gln variant may not impact protein function (PMID: 21458570). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autism, seizures, and intellectual disability.
CeGaT Center for Human Genetics Tuebingen	RCV000710154	SCV002544331	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	KCNJ10: BS1, BS2
Genetic Services Laboratory, University of Chicago	RCV000117319	SCV000151500	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.