Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003318500 | SCV004022329 | uncertain significance | Monogenic diabetes | 2023-07-17 | reviewed by expert panel | curation | The c.1136C>G variant in the glucokinase gene, GCK, causes an amino acid change of alanine to proline at codon 379 (p.(Ala379Gly)) of NM_000162.5. GCK is defined by the ClinGen MDEP VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0 0.922, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant, c.1136C>A p.Ala379Glu, has been classified as likely pathogenic by the ClinGen MDEP VCEP (PM5_Supporting). This variant was identified in an individual undergoing clinical testing, however, there was insufficient clinical information to evaluate for PP4 (ClinVar ID: 447382). In summary, this variant meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.2.0, approved 6/7/2023): PP2, PP3, PM2_Supporting, PM5_supporting. |
Athena Diagnostics Inc | RCV000518241 | SCV000613400 | uncertain significance | not provided | 2020-08-19 | criteria provided, single submitter | clinical testing |