Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001843362 | SCV002102531 | pathogenic | Monogenic diabetes | 2022-03-04 | reviewed by expert panel | curation | The c.1A>T variant in the HNF1 homeobox A gene, HNF1A, results in the loss of the initiation codon (p.Met1Leu) of transcript NM_000545.8. By altering the start codon of the coding sequence, this variant is predicted to cause a truncated or absent protein in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). 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, sulfonylurea-responsive, and antibody negative) (PP4_Moderate; internal lab contributor). In summary, c.1A>T 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 9/30/2021): PVS1, PM2_Supporting and PP4_Moderate. |
Eurofins Ntd Llc |
RCV000595936 | SCV000709302 | pathogenic | not provided | 2017-06-27 | criteria provided, single submitter | clinical testing |