Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002250369 | SCV002520667 | uncertain significance | Monogenic diabetes | 2022-05-04 | reviewed by expert panel | curation | The c.1819dupC variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 607 (NM_000545.8), adding 42 novel amino acids before encountering a stop codon (p.(Gln607ProfsTer42). While this variant, located in exon 10 of 10, is not predicted to result in nonsense mediated decay of the transcript, it will significantly disrupt the transactivation domain of the protein and add 16 additional amino acids to the end of the protein (PVS1_Strong). Additionally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1819dupC meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PVS1_Strong, PM2_Supporting. |
Clinical Genomics, |
RCV002329205 | SCV002601634 | uncertain significance | 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 rs1555212747 with MODY3. | |
Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000505657 | SCV000599869 | pathogenic | Maturity-onset diabetes of the young type 3 | 2017-04-20 | no assertion criteria provided | clinical testing |