Submissions for variant NM_000458.4(HNF1B):c.1578C>G (p.Ser526=)

gnomAD frequency: 0.00009  dbSNP: rs751225159

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000593911	SCV000707892	uncertain significance	not provided	2017-04-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001124746	SCV001283733	likely benign	Renal cysts and diabetes syndrome	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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002465734	SCV002754394	uncertain significance	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia. However no sufficient evidence is found to ascertain the role of this particular variant rs751225159, yet.
GeneDx	RCV000593911	SCV004039975	uncertain significance	not provided	2023-03-31	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000593911	SCV004635963	likely benign	not provided	2023-08-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000593911	SCV001977950	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000593911	SCV001980478	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945429	SCV004762838	likely benign	HNF1B-related disorder	2021-03-29	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).