Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002795099 | SCV003020589 | uncertain significance | not provided | 2024-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 288 of the HNF1A protein (p.Gly288Arg). This variant is present in population databases (rs539507291, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of maturity-onset diabetes of the young (PMID: 35733065). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1982702). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt HNF1A protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on HNF1A function (PMID: 32910913). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV005008743 | SCV005634475 | 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 | 2024-04-23 | criteria provided, single submitter | clinical testing |