Submissions for variant NM_000458.4(HNF1B):c.660T>C (p.Asp220=)

gnomAD frequency: 0.00008  dbSNP: rs779375959

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001248887	SCV001422567	benign	Maturity onset diabetes mellitus in young	2020-01-22	criteria provided, single submitter	curation	The c.660T>C (p.Asp220=) variant in HNF1B has not been previously reported in individuals with MODY but has been identified in 0.01% (18/129182) of European (non-Finnish) chromosomes and 0.01% (1/10370) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs779375959). This variant has been seen in the general population at a frequency high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, this variant meets criteria to be classified as benign for MODY in an autosomal dominant manner based on the frequency in the general population. ACMG/AMP Criteria applied: BA1 (Richards 2015).
Genetic Services Laboratory, University of Chicago	RCV001819954	SCV002065105	likely benign	not specified	2017-10-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002069316	SCV002394951	likely benign	not provided	2023-11-20	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002491851	SCV002806497	likely benign	Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma	2021-08-03	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001248887	SCV002605434	likely risk allele	Maturity onset diabetes mellitus in young		flagged submission	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 rs779375959, yet.
PreventionGenetics, part of Exact Sciences	RCV003945947	SCV004761246	likely benign	HNF1B-related disorder	2024-02-26	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).