Submissions for variant NM_000525.4(KCNJ11):c.1154C>G (p.Ser385Cys)

gnomAD frequency: 0.00987  dbSNP: rs41282930

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030102	SCV000052757	likely benign	Neonatal diabetes mellitus	2011-08-18	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Genetic Services Laboratory, University of Chicago	RCV000146102	SCV000193319	benign	not specified	2013-10-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000146102	SCV000304665	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000342808	SCV000369149	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	RCV000395172	SCV000369150	uncertain significance	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, 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	RCV000284629	SCV000369151	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	RCV000445546	SCV000537076	benign	Monogenic diabetes	2019-02-22	criteria provided, single submitter	research	ACMG criteria: BA1 (2.4% in Africans in gnomAD) + BS2 (125 controls and 75 cases in T2D) (removed BP4 because of conflicting evidence: BP4 [4 predictors]; PP3 [6 predictors], REVEL=0.369)=benign
Athena Diagnostics	RCV000712157	SCV000842582	benign	not provided	2017-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000712157	SCV001102130	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000395172	SCV001652876	likely benign	Hyperinsulinemic hypoglycemia, familial, 2	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000712157	SCV001843300	benign	not provided	2021-02-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22289434, 21968738, 24068186, 21119644, 25998140, 24698822, 28460053, 31149081, 25247988, 28587604, 8897013, 10338089, 15504982, 15115830, 29396286)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226658	SCV002505477	uncertain significance	Maturity onset diabetes mellitus in young		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. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of rs41282930 variant in Diabetes Mellitus yet.