Submissions for variant NM_000525.4(KCNJ11):c.801C>G (p.Leu267=)

gnomAD frequency: 0.01521  dbSNP: rs5216

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000146118	SCV000193335	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000146118	SCV000304668	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000146118	SCV000341479	benign	not specified	2016-05-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000381795	SCV000369170	benign	Diabetes mellitus, transient neonatal, 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000576711	SCV000369171	uncertain significance	Hyperinsulinemic hypoglycemia, familial, 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000351492	SCV000369172	benign	Maturity-onset diabetes of the young type 13	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000576711	SCV000677331	benign	Hyperinsulinemic hypoglycemia, familial, 2	2017-05-19	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000576711	SCV001653344	likely benign	Hyperinsulinemic hypoglycemia, familial, 2	2021-05-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001520976	SCV001730215	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000381795	SCV001749036	likely benign	Diabetes mellitus, transient neonatal, 3	2021-07-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001533237	SCV001749037	likely benign	Diabetes mellitus, permanent neonatal 2	2021-07-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000576711	SCV001749038	likely benign	Hyperinsulinemic hypoglycemia, familial, 2	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001520976	SCV001861330	benign	not provided	2020-11-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21765448, 16670688, 14871556, 25972930, 22512215)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226688	SCV002505463	benign	Type 2 diabetes mellitus		criteria provided, single submitter	research	Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. This does not cause any sensitivity towards mild hypoglycemia, an adverse effect of Sulfonylureas treatment. rs5216 is also known to be associated with increased risk of T2DM.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001520976	SCV004562827	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV003993826	SCV004812474	benign	Hyperinsulinemic hypoglycemia	2023-05-04	criteria provided, single submitter	clinical testing	European Non-Finnish population allele frequency is 2.25% (rs5216, 4238/251358 alleles, 45 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1
Natera, Inc.	RCV001275133	SCV001459964	benign	Permanent neonatal diabetes mellitus	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001520976	SCV001799163	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001520976	SCV001926866	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000146118	SCV001956344	benign	not specified		no assertion criteria provided	clinical testing