ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1719del (p.Ser574fs)

dbSNP: rs2135851518
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002260477 SCV002540101 pathogenic Monogenic diabetes 2022-06-15 reviewed by expert panel curation The c.1719delC variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 574 of NM_000545.8, adding 86 novel amino acids before encountering a stop codon (p.(Ser574AlafsTer86)). While this variant, located in exon 9 of 10, is not predicted to result in nonsense mediated decay of the transcript, it will significantly disrupt the transactivation domain of the protein (PVS1). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and sensitive to sulfonylurea) (PP4_Moderate; internal lab contributor). In summary, c.1719delC meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PVS1, PP4_Moderate, PM2_Supporting.

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