ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.34G>T (p.Gly12Cys) (rs121913250)

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Total submissions: 10
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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 cancer 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 Adenocarcinoma of stomach 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

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