ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.34G>T (p.Gly12Cys)

dbSNP: rs121913250
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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).
Database of Curated Mutations (DoCM) RCV000440380 SCV000503727 pathogenic Non-small cell lung carcinoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422738 SCV000503728 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433830 SCV000503729 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444830 SCV000503730 pathogenic Melanoma 2014-12-26 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422059 SCV000503731 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432311 SCV000503732 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445013 SCV000503733 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425805 SCV000503734 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435186 SCV000503735 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Druker Lab, Oregon Health and Sciences University RCV002291497 SCV002583833 pathogenic Chronic myelogenous leukemia, BCR-ABL1 positive 2022-10-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.