ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.35G>C (p.Gly12Ala) (rs121913237)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000434113 SCV000503709 pathogenic Cutaneous melanoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444670 SCV000503710 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427550 SCV000503711 pathogenic Non-small cell lung cancer 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433455 SCV000503712 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444591 SCV000503713 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426950 SCV000503714 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437165 SCV000503715 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418647 SCV000503716 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425963 SCV000503717 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000380895 SCV000330301 pathogenic not provided 2017-02-01 criteria provided, single submitter clinical testing The G12A missense varant in the NRAS gene has been reported previously as a somatic mutation in association with several different types of cancer and primarily affected haematopoietic and lymphoid tissues (Catalogue of Somatic Mutations in Cancer; ClinVar SCV000258463.2: Landrum et al. 2014). G12A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G12A is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. The glycine codons 12 and 13 of RAS proteins within the RAS/MAPK pathway are functionally important for GDP/GTP binding and are considered hot spots" for pathogenic variants (Wey et al. 2013; Gripp et al. 2012). Missense variants in the same codon (G12S) and in a nearby residue (G13D) have been reported in the Human Gene Mutation Database in association with NRAS-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein."
Hospital of the University of Pennsylvania,Center for Personalized Diagnostics RCV000203450 SCV000258463 pathogenic Myelodysplastic syndrome progressed to acute myeloid leukemia 2016-01-08 criteria provided, single submitter clinical testing Activating mutation

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