Submissions for variant NM_000458.4(HNF1B):c.345-11T>G

gnomAD frequency: 0.00001  dbSNP: rs200782591

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001248987	SCV001422829	uncertain significance	Maturity onset diabetes mellitus in young	2020-01-22	criteria provided, single submitter	curation	The c.345-11T>G variant in HNF1B has not been previously reported in individuals with MODY and has been identified in 0.002% (2/102988) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200782591). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.345-11T>G variant is uncertain. ACMG/AMP Criteria applied: PM2, BP7, BP4 (Richards 2015).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV001248987	SCV002738640	uncertain risk allele	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 rs200782591, yet.