Submissions for variant NM_000162.5(GCK):c.148dup (p.His50fs)

dbSNP: rs886041690

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000320367	SCV000330420	pathogenic	not provided	2018-03-28	criteria provided, single submitter	clinical testing	The c.148dupC pathogenic variant in the GCK gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.148dupC variant causes a frameshift starting with codon Histidine 50, changes this amino acid to a Proline residue and creates a premature Stop codon at position 2 of the new reading frame, denoted p.His50ProfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002465607	SCV002605383	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 rs886041690 in MODY, yet.