Submissions for variant NM_001042413.2(GLIS3):c.1536C>A (p.Asp512Glu)

gnomAD frequency: 0.01645  dbSNP: rs148199056

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000117147	SCV000151310	benign	not specified	2013-12-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000331842	SCV000480273	benign	Neonatal diabetes mellitus with congenital hypothyroidism	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.
Eurofins Ntd Llc (ga)	RCV000117147	SCV000702857	benign	not specified	2016-10-18	criteria provided, single submitter	clinical testing
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174470	SCV001337609	benign	Monogenic diabetes	2018-08-10	criteria provided, single submitter	research	ACMG criteria: (REVEL = 0.123, PP3/3 predictors, BP4,7 predictors = conflicting evidence, not using), BA1 (1.7% overall MAF in gnomAD; 3.97% in EF, 2% in SA and ENF pop), BS2 (58 homozygotes in gnomAD)=benign
Invitae	RCV001515726	SCV001723864	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001515726	SCV001941924	benign	not provided	2021-04-19	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28444304, 31415576)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226664	SCV002505504	benign	Diabetes mellitus		criteria provided, single submitter	research	Mutations in GLIS3 gene predisposes to neonatal diabetes mellitus with an extra pancreatic manifestation of hypothyroidism. rs148199056 (p.D512E) also predisposes to early onset diabetes in adults. However, Its significance in predisposition to MODY remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV001515726	SCV002585064	benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	GLIS3: BP4, BS1, BS2
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000117147	SCV001799751	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000117147	SCV001922386	benign	not specified		no assertion criteria provided	clinical testing