Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158979 | SCV000208918 | pathogenic | not provided | 2012-06-02 | criteria provided, single submitter | clinical testing | This variant is denoted as p.Gly12Cys (GGT>TGT): c.34 G>T in exon 2 of NRAS. The G12C missense mutation has not be reported as a benign polymorphism or as a disease-causing mutation, to our knowledge. The G12C missense change is a non-conservative amino acid substitution with a non-polar residue (Gly) being replaced by a polar residue (Cys). The position at which this substitution occurs is highly conserved in the protein and the gain of a Cysteine residue may affect disulfide bond formation in the protein. A different missense mutation this codon (G12V) has been reported previously as a somatic mutation in association with several different types of cancer (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010), primarily in haematopoietic and lymphoid tissues. Another missense mutation at a neighboring codon (G13D) has been reported as a germline mutation (Filippi et al., 2009; Oliviera et al., 2007). In Filippi et al., the patient with the G13D mutation was described as having dysmorphic features (including macrocephaly, bilateral epicanthal folds and cafe-au-lait spots) in addition to clinical and hematological features consistent with a diagnosis of juvenile myelomonocytic leukemia (JMML) (Filippi et al., 2009). The presence of the G12C mutation is consistent with a diagnosis of an NRAS-related disorder and the reported diagnosis of JMML. The variant is found in NOONAN panel(s). |
| Druker Lab, |
RCV002291497 | SCV002583833 | pathogenic | Chronic myelogenous leukemia, BCR-ABL1 positive | 2022-10-10 | no assertion criteria provided | clinical testing |