ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.866A>G (p.Tyr289Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MGZ Medical Genetics Center RCV002290240 SCV002579451 likely pathogenic Maturity-onset diabetes of the young type 2 2021-08-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003560936 SCV004295153 pathogenic not provided 2022-12-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the Tyr289His amino acid residue in GCK. Other variant(s) that disrupt this residue have been observed in individuals with GCK-related conditions (PMID: 19564454), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1709898). This missense change has been observed in individuals with maturity-onset diabetes of the young (PMID: 19790256, 22335469, 22761713, 23433541, 28012402; personal communication). 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 tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 289 of the GCK protein (p.Tyr289Cys).

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