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

dbSNP: rs121913250

Total submissions: 11

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