Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001941538 | SCV002236714 | pathogenic | not provided | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr289*) in the GCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCK are known to be pathogenic (PMID: 7553875, 9867845, 14578306, 24323243, 25015100). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 19410318). ClinVar contains an entry for this variant (Variation ID: 1453774). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002370606 | SCV002685782 | pathogenic | Maturity onset diabetes mellitus in young | 2016-09-12 | criteria provided, single submitter | clinical testing | The p.Y289* pathogenic mutation (also known as c.867T>A), located in coding exon 8 of the GCK gene, results from a T to A substitution at nucleotide position 867. This changes the amino acid from a tyrosine to a stop codon within coding exon 8. A different nucleotide substitution (c.867T>G) resulting in the same stop codon (p.Y289*) was identified in two unrelated Spanish individuals with maturity-onset diabetes of the young (Solera J et al. Diabetes Res. Clin. Pract., 2009 Jul;85:20-3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |