ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.169del (p.Leu57fs)

dbSNP: rs193922588
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002222003 SCV002499477 likely pathogenic Monogenic diabetes 2022-04-03 reviewed by expert panel curation The c.169delC variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 57 (NM_000545.8), adding 98 novel amino acids before encountering a stop codon (p.(Leu57TrpfsTer98)). This variant, located in biologically-relevant exon 1 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) and is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was previously reported in ClinVar, but no clinical information was provided, so PP4 could not be applied. In summary, c.142delG 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 9/30/21): PVS1, PM2_Supporting.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030489 SCV000053159 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 RCV002326703 SCV002601683 likely pathogenic 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 rs193922588 with MODY3.

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