ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1506_1507dup (p.Tyr503fs)

dbSNP: rs193922582
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002250353 SCV002520659 likely pathogenic Monogenic diabetes 2022-05-03 reviewed by expert panel curation The c.1506_1507dupCT variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 503 (NM_000545.8), adding 29 novel amino acids before encountering a stop codon (p.Tyr503SerfsTer29). This variant, located in biologically-relevant exon 8 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1506_1507dupCT meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PVS1, PM2_Supporting.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030483 SCV000053153 likely pathogenic Maturity-onset diabetes of the young type 3 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002463433 SCV002604940 uncertain risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs193922582 with MODY3.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.