Submissions for variant NM_000162.5(GCK):c.148C>T (p.His50Tyr)

dbSNP: rs1562719705

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Unidad de Genómica Médica UC, Pontificia Universidad Católica de Chile	RCV000778070	SCV000902454	pathogenic	Maturity-onset diabetes of the young type 2	2016-03-07	criteria provided, single submitter	research	The index case is a patient who presented severe neonatal hyperglycemia (831 mg/dl, without ketosis) requiring continuous infusion of insulin, which was suspended after 48 hours with normalization of blood glucose. Subsequently, continuous glucose monitoring at 4 months of age revealed 47% of tissue glucose levels above 140 mg/dl, with fasting glucose levels between 120 and 166 mg/dl. The genetic analysis revealed a previously reported mutation in heterozygous state of the GCK gene (c.148C>T; p.His50Tyr). This mutation was also identified in more than one affected relative in the last two generations, with a transmission pattern suggestive of dominant inheritance. GCK gene sequencing led to a correct molecular diagnosis of MODY 2 while bioinformatic analysis indicated the possible molecular causes of the enzyme dysfunction. This variant p.(His50Tyr) has been also described by Massa et al., 2001 (PMID: 11508276) and Mantovani et al., 2003 (PMID: 12955723) with a pathogenic status for MODY 2.
Genetic Services Laboratory, University of Chicago	RCV001816832	SCV002072074	pathogenic	not provided	2017-08-24	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002332563	SCV002601607	likely pathogenic	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 rs1562719705 in MODY, yet.