Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000992046 | SCV001144010 | likely pathogenic | not provided | 2025-03-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features associated with this gene. This variant appears to be associated with disease in at least one family. Polyphen and MutationTaster predict this amino acid change may be damaging to the protein. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. |
| MGZ Medical Genetics Center | RCV002290505 | SCV002580327 | likely pathogenic | Maturity-onset diabetes of the young type 2 | 2021-11-17 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002290505 | SCV004813481 | likely pathogenic | Maturity-onset diabetes of the young type 2 | 2024-02-26 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.1340G>C (p.Arg447Pro) results in a non-conservative amino acid change located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. This alters a highly conserved residue (HGMD) in which other missense changes have been found in association with MODY, one of which is classified as pathogenic by our lab. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 625660 control chromosomes (gnomAD v4.0). c.1340G>C has been reported in the literature in individuals affected with Maturity Onset Diabetes Of The Young 2/Neonatal Diabetes Mellitus (Shammas_2013, Gaal_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23890519, 34440516). ClinVar contains an entry for this variant (Variation ID: 804842). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV000992046 | SCV005201992 | likely pathogenic | not provided | 2024-02-07 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 26587058, 34440516, 23890519) |
| Fulgent Genetics, |
RCV005036262 | SCV005666174 | likely pathogenic | Type 2 diabetes mellitus; Hyperinsulinism due to glucokinase deficiency; Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitus 1 | 2024-04-08 | criteria provided, single submitter | clinical testing |