ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.181C>A (p.Gln61Lys) (rs121913254)

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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000434388 SCV000503649 pathogenic Cutaneous melanoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444538 SCV000503650 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426976 SCV000503651 likely pathogenic Nasopharyngeal Neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436806 SCV000503652 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443974 SCV000503653 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425440 SCV000503654 pathogenic Non-small cell lung cancer 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436588 SCV000503655 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418907 SCV000503656 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428264 SCV000503657 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435041 SCV000503658 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418269 SCV000503659 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428499 SCV000503660 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441348 SCV000503661 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423656 SCV000503662 not provided Neuroblastoma 2016-03-10 no assertion provided literature only
Database of Curated Mutations (DoCM) RCV000431313 SCV000503663 likely pathogenic Adrenocortical carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441559 SCV000503664 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423012 SCV000503665 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433274 SCV000503666 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444882 SCV000503667 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Invitae RCV000696329 SCV000824885 uncertain significance Rasopathy 2018-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 61 of the NRAS protein (p.Gln61Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). While this variant has been published in the literature (PMID: 23392294), it has not been reported in the germline of an individual with NRAS-related disease. ClinVar contains an entry for this variant (Variation ID: 73058). This variant has been reported as a recurrent variant in melanoma tumors (PMID: 23392294), colorectal tumors (PMID: 27050078, 23400451), thyroid tumors (PMID: 28780248), squamous cell lung tumors (PMID: 25348872), neuroblastoma tumors (PMID: 26821351), and gynecological tumors (PMID: 24671188). Experimental studies have shown that this missense change p.Gln61Lys, results in cytoskeletal changes in melanocyte cell lines, reduces apoptosis, and results in hyperpigmented skin in transgenic mice who develop cutaneous metastasizing melanoma (PMID: 22718121, 18668139, 15899789). However, in a thyroid epithelial cell line, this variant alone resulted in zero tumor instances (PMID: 10821536). In zebrafish, expression of human NRAS p.Q61K in melanocytes results in the growth of pigmented lesions that rarely progress to melanoma. (PMID: 24148783). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000114746 SCV000148629 pathogenic Congenital giant melanocytic nevus 2013-09-01 no assertion criteria provided literature only
OMIM RCV000144964 SCV000191991 pathogenic Neurocutaneous melanosis 2013-09-01 no assertion criteria provided literature only
Oxford Haemato-Oncology Service,Oxford University Hospitals NHS Foundation Trust RCV000626456 SCV000734846 drug response RAS Inhibitor response 2017-11-27 no assertion criteria provided clinical testing
Yale Center for Mendelian Genomics,Yale University RCV000662267 SCV000784595 likely pathogenic Vascular Tumors Including Pyogenic Granuloma 2015-02-19 no assertion criteria provided literature only

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