ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.666C>T (p.Val222=)

gnomAD frequency: 0.00011  dbSNP: rs193922318
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000516740 SCV000052560 benign not specified 2023-10-10 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000516740 SCV000613447 benign not specified 2017-04-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000927962 SCV001073563 benign not provided 2018-09-10 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000029905 SCV001324100 uncertain significance Maturity-onset diabetes of the young type 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001162165 SCV001324101 uncertain significance Hyperinsulinism due to glucokinase deficiency 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001162166 SCV001324102 uncertain significance Transient Neonatal Diabetes, Recessive 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001164186 SCV001326293 uncertain significance Permanent neonatal diabetes mellitus 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics RCV002362598 SCV002661754 uncertain significance Maturity onset diabetes mellitus in young 2023-03-20 criteria provided, single submitter clinical testing The c.666C>T variant (also known as p.V222V), located in coding exon 6 of the GCK gene, results from a C to T substitution at nucleotide position 666. This nucleotide substitution does not change the at codon 222. This variant was previously identified in one individual with maturity-onset diabetes of the young. In vitro studies using mini-gene constructs showed this alteration can introduce an alternate splice donor site that would result in the deletion of 16 nucleotides from exon 6 in the RNA transcript (Igudin E et al. Mol. Biol. (Mosk.) 2014;48(2):288-94). In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site. This nucleotide position is poorly conserved in available vertebrate species with thymine being the reference nucleotide in several species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
New York Genome Center RCV003335057 SCV004046452 uncertain significance Type 2 diabetes mellitus; Hyperinsulinism due to glucokinase deficiency; Maturity-onset diabetes of the young type 2 2023-01-14 criteria provided, single submitter clinical testing

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