Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001249070 | SCV001423018 | uncertain significance | Maturity-onset diabetes of the young type 3 | 2020-01-22 | criteria provided, single submitter | curation | The p.Ala311Asp variant in HNF1A has been reported in 4 Chinese relatives from 1 family with only 1 individual with MODY and 1 European individual with MODY (PMID: 15657605, 18003757), and has been identified in 0.01% (2/16140) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs757574765). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PS4_supporting (Richards 2015). |
Prevention |
RCV003399020 | SCV004105692 | uncertain significance | HNF1A-related disorder | 2023-06-20 | criteria provided, single submitter | clinical testing | The HNF1A c.932C>A variant is predicted to result in the amino acid substitution p.Ala311Asp. This variant has been reported in several individuals with maturity onset diabetes of the young, type 3 (MODY3); however, pathogenicity of the variant was not conclusively established in any of the reports (Xu et al. 2005. PubMed ID: 15657605; Bellanné-Chantelot et al. 2008. PubMed ID: 18003757; Rama Chandran et al. 2018. PubMed ID: 30181854; Ma et al. 2020. PubMed ID: 32238361). This variant is reported in 0.012% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-121432185-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Fulgent Genetics, |
RCV005012690 | SCV005634482 | uncertain significance | Diabetes mellitus type 1; Type 1 diabetes mellitus 20; Maturity-onset diabetes of the young type 3; Type 2 diabetes mellitus; Hepatic adenomas, familial; Nonpapillary renal cell carcinoma | 2024-05-21 | criteria provided, single submitter | clinical testing |