Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000711772 | SCV000842168 | uncertain significance | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000711772 | SCV002069250 | likely pathogenic | not provided | 2020-04-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000711772 | SCV003440026 | likely pathogenic | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 122 of the GCK protein (p.Leu122Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal dominant maturity onset diabetes of the young (PMID: 11508276, 32468610). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 585919). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Leu122 amino acid residue in GCK. Other variant(s) that disrupt this residue have been observed in individuals with GCK-related conditions (PMID: 15928245, 31905448), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |