ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.364C>G (p.Leu122Val)

dbSNP: rs1554335616
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Total submissions: 3
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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, University of Chicago 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.

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