Submissions for variant NM_000525.4(KCNJ11):c.808C>G (p.Leu270Val)

gnomAD frequency: 0.03859  dbSNP: rs1800467

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000146119	SCV000193336	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000146119	SCV000304669	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000146119	SCV000340114	benign	not specified	2016-03-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000372639	SCV000369164	benign	Maturity-onset diabetes of the young type 13	2018-01-13	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	RCV000576834	SCV000369165	likely benign	Hyperinsulinemic hypoglycemia, familial, 2	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000323784	SCV000369166	benign	Diabetes mellitus, transient neonatal, 3	2018-01-13	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.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445429	SCV000537077	benign	Monogenic diabetes	2019-02-22	criteria provided, single submitter	research	ACMG criteria: BA1 (4% overall MAF in gnomAD, 11% MAF in EF, 6.8% in AJ), BS2 (936 cases and 916 controls in T2DM): benign (Revel score 0.344 + PP3 (4 predictors) + BP4 (5 predictors): conflicing evidence, not using; no longer using BP6)
Athena Diagnostics	RCV000576834	SCV000677332	benign	Hyperinsulinemic hypoglycemia, familial, 2	2017-05-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001516639	SCV001724944	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000323784	SCV001749033	benign	Diabetes mellitus, transient neonatal, 3	2021-07-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV001533236	SCV001749034	benign	Diabetes mellitus, permanent neonatal 2	2021-07-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000576834	SCV001749035	benign	Hyperinsulinemic hypoglycemia, familial, 2	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001516639	SCV001872360	benign	not provided	2018-09-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25972930)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226426	SCV002505382	uncertain significance	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	Mutations in the KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which is responsive to oral sulfonylureas. However, the variant rs1800467 might not pose increased sensitivity to Type II Diabetes by itself but in combination with other variants in KCNJ11 or INS and HNF1A increase predisposition to insulin resistance.
Natera, Inc.	RCV001275132	SCV001459963	benign	Permanent neonatal diabetes mellitus	2020-09-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000146119	SCV001744803	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000146119	SCV001797755	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001516639	SCV001927431	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000146119	SCV001955891	benign	not specified		no assertion criteria provided	clinical testing