Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV001665505 | SCV001880085 | uncertain significance | not provided | 2020-09-23 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001665505 | SCV002142453 | pathogenic | not provided | 2022-02-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg203 amino acid residue in HNF1A. Other variant(s) that disrupt this residue have been observed in individuals with HNF1A-related conditions (PMID: 21168233, 30293189, 31363388), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HNF1A protein function. ClinVar contains an entry for this variant (Variation ID: 1256577). This missense change has been observed in individual(s) with autosomal dominant maturity-onset diabetes of the young (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 203 of the HNF1A protein (p.Arg203Leu). |