Description
Variant summary: GCK c.1130G>T (p.Arg377Leu) results in a non-conservative amino acid change located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 234572 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1130G>T has been reported in the literature in individuals affected with features of Monogenic Diabetes (example, Osbak_2009, Borowiec_2012, Ma_2019, Zhou_2020, unpublished observations from the Clingen MODY expert panel). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21348868, 30245511, 19790256, 32375122). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |