Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000987868 | SCV001137352 | pathogenic | Maturity-onset diabetes of the young type 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Geisinger Clinic, |
RCV000987868 | SCV002562164 | pathogenic | Maturity-onset diabetes of the young type 2 | 2022-08-02 | criteria provided, single submitter | research | PVS1, PM2, PP1_Strong, PS4, PP4 |
| Ambry Genetics | RCV002409317 | SCV002710949 | pathogenic | Maturity onset diabetes mellitus in young | 2019-10-24 | criteria provided, single submitter | clinical testing | The p.Y61* pathogenic mutation (also known as c.183C>A), located in coding exon 2 of the GCK gene, results from a C to A substitution at nucleotide position 183. This changes the amino acid from a tyrosine to a stop codon within coding exon 2. This mutation was detected in a homozygous permanent neonatal diabetes case, as well as in additional heterozygous family members with hyperglycemia (Rubio-Cabezas O et al. Pediatr Diabetes, 2008 Jun;9:245-9). This mutation has also been reported in a maturity-onset diabetes of the young (MODY) cohort, although clinical details were limited (Estalella I et al. Clin. Endocrinol. (Oxf), 2007 Oct;67:538-46). In addition to the clinical data presented in the literature, 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. |
| Invitae | RCV002549692 | SCV003439956 | pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr61*) 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 autosomal dominant maturity onset diabetes of the young or autosomal recessive permanent neonatal diabetes (PMID: 17573900, 18298419, 23009393). ClinVar contains an entry for this variant (Variation ID: 802309). For these reasons, this variant has been classified as Pathogenic. |