ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1340G>A (p.Arg447Gln)

dbSNP: rs1131691416
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494422 SCV000582084 pathogenic not provided 2022-06-30 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27271189, 19790256, 28012402, 14517946, 14517956, 28170077, 16965331, 22773699, 24097065, 24578721, 33046911, 32533152, 20337973, 34440516, 26587058)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001290675 SCV001478807 pathogenic Maturity-onset diabetes of the young type 2 2021-01-27 criteria provided, single submitter clinical testing Variant summary: GCK c.1340G>A (p.Arg447Gln) results in a conservative amino acid change located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 241628 control chromosomes (gnomAD). c.1340G>A has been reported in the literature in multiple individuals with a suspected clinical diagnosis of or affected with Maturity Onset Diabetes of the Young 2 (example: Santana_2017, Flanick_2013, Vits_2006, Pruhova_2010, Thomson_2003). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genetic Services Laboratory,University of Chicago RCV000494422 SCV002069076 likely pathogenic not provided 2018-01-22 criteria provided, single submitter clinical testing

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