Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000787182 | SCV000926112 | pathogenic | Renal cysts and diabetes syndrome | 2019-07-06 | criteria provided, single submitter | literature only | |
Broad Center for Mendelian Genomics, |
RCV000787182 | SCV003761367 | likely pathogenic | Renal cysts and diabetes syndrome | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Gln176Ter variant in HNF1B was identified by our study in one individual with cystic kidney disease. The p.Gln176Ter variant in HNF1B has been previously reported in one individual with HNF1B-associated kidney disease (PMID: 15930087). This variant has also been reported in ClinVar (Variation ID: 635675) and has been interpreted as pathogenic by the Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 176, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the HNF1B gene is an established disease mechanism in autosomal dominant HNF1B-associated kidney disease. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for HNF1B-associated kidney disease. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015). |