Submissions for variant NM_000458.4(HNF1B):c.61dup (p.Val21fs)

dbSNP: rs2034124973

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001251467	SCV001427167	pathogenic	Renal cysts and diabetes syndrome	2019-01-03	criteria provided, single submitter	clinical testing	A heterozygous frameshift duplication variant, NM_000458.3(HNF1B):c.61dupG, has been identified in exon 1 of 9 of the HNF1B gene. This duplication is predicted to create a frameshift starting at amino acid position 21, introducing a stop codon 67 residues downstream (NP_000449.1(HNF1B):p.(Val21Glyfs*67)). This variant is predicted to result in loss of protein function through nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G). This variant has not been previously reported in clinical cases, however, other loss of function variants have previously been reported pathogenic in this gene (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464421	SCV002640389	likely pathogenic	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 rs2034124973, yet.