Submissions for variant NM_000162.5(GCK):c.1280T>G (p.Val427Gly)

dbSNP: rs1562712097

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel	RCV004527395	SCV005040670	uncertain significance	Monogenic diabetes	2024-04-27	reviewed by expert panel	curation	The c.1280T>G variant in the glucokinase gene, GCK, causes an amino acid change of valine to glycine at codon 427 (p.(Val427Gly)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.976, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a phenotype suggestive of GCK-hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (internal lab contributors). In summary, c.1280T>G meets the criteria to be classified as uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PM2_supporting, PP2, PP3.
Athena Diagnostics	RCV000711762	SCV000842156	uncertain significance	not provided	2018-03-19	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002463456	SCV002604996	likely risk allele	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1562712097 in MODY, yet.