Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV004720201 | SCV005326350 | likely pathogenic | Maturity-onset diabetes of the young type 1 | criteria provided, single submitter | clinical testing | The p.Cys90Trp variant results in substitution of the cysteine at amino acid position 90 with a tryptophan. The p.Cys90 position is located in one of two zinc-finger domains making up the DNA binding domain in the HNF4A protein. The cysteine at amino acid position 90 is highly conserved. In silico tools predict the p.Cys90Trp variant to be damaging. Nearby variants in the same domain, including the p.Cys93Tyr variant (ClinVar Variation ID: 2502290), have been observed among individuals with HNF4A-related diabetes. To our knowledge, the p.Cys90Trp variant is absent from patient databases and the medical literature, as well as large population studies (gnomAD v4.0.0). |