Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002222073 | SCV002499551 | uncertain significance | Monogenic diabetes | 2022-04-14 | reviewed by expert panel | curation | The c.865C>T variant in the e.g. HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to serine at codon 289 (p.(Pro289Ser)) of NM_000545.8. This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to age of diagnosis over 35; therefore, PP4 cannot be applied (internal lab contributors). Two other missense variants, c.866C>A (p.Pro289His) and c.866C>G (p.Pro289Arg), have been classified as VUS by the ClinGen MDEP; therefore PM5 will not be applied. In summary, c.865C>T 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): PM2_Supporting. |
Gene |
RCV001755274 | SCV002005363 | uncertain significance | not provided | 2020-02-07 | criteria provided, single submitter | clinical testing | Has been reported in one patient with MODY; however further evidence such as segregation or functional studies, were not specified in this report (Bellanne-Chantelot etla., 2008); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18003757) |
Fulgent Genetics, |
RCV002488608 | SCV002779536 | 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 | 2024-05-31 | criteria provided, single submitter | clinical testing |