Submissions for variant NM_002524.5(NRAS):c.182A>G (p.Gln61Arg)

dbSNP: rs11554290

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine	RCV000037574	SCV000061232	pathogenic	Non-small cell lung carcinoma	2011-08-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000413804	SCV000490986	pathogenic	not provided	2015-05-04	criteria provided, single submitter	clinical testing	The Q61R missense variant in the NRAS gene has been reported previously in association with NRAS-related disorders (Rivera et al., 2010; Wong et al., 2014). Q61R 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. Functional studies of the Q61R variant have shown that it leads to constitutive ERK signaling and thus dysregulation of the MAPK pathway (Wong et al., 2014). In addition, missense variants in nearby residues (T50I, G60E) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein.
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV000413804	SCV002525697	pathogenic	not provided	2021-09-03	criteria provided, single submitter	clinical testing	This is a recurrent pathogenic variant that has been reported previously in multiple individuals with kaposiform lymphangiomatosis (KLA), as well as an individual with a generalized lymphatic anomaly (GLA), also known as diffuse lymphangiomatosis (PMID: 30542204, PMID: 31511039, PMID: 29397482). This change is also reported as an oncogenic variant found in multiple tumor types, especially melanoma (COSMIC and cBioPortal Databases). This variant is not present in large population cohorts (Genome Aggregation Database v2.1.1). The p.Gln61Arg variant leads to constitutive activation of the NRAS protein (PMID: 30542204, PMID: 29397482).
OMIM	RCV000014914	SCV000035170	pathogenic	Thyroid cancer, nonmedullary, 2	2014-01-15	no assertion criteria provided	literature only
OMIM	RCV000032847	SCV000056616	pathogenic	Epidermal nevus	2014-01-15	no assertion criteria provided	literature only
OMIM	RCV000114744	SCV000148627	pathogenic	Large congenital melanocytic nevus	2014-01-15	no assertion criteria provided	literature only
OMIM	RCV000114745	SCV000148628	pathogenic	Neurocutaneous melanocytosis	2014-01-15	no assertion criteria provided	literature only
OMIM	RCV000148032	SCV000195534	pathogenic	Linear nevus sebaceous syndrome	2014-01-15	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000424960	SCV000503611	pathogenic	Melanoma	2016-03-10	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000435687	SCV000503612	pathogenic	Neoplasm of the large intestine	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000037574	SCV000503613	pathogenic	Non-small cell lung carcinoma	2014-10-02	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000424721	SCV000503614	likely pathogenic	Lung adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000438052	SCV000503615	likely pathogenic	Glioblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000420832	SCV000503616	likely pathogenic	B-cell chronic lymphocytic leukemia	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000430593	SCV000503617	likely pathogenic	Nasopharyngeal neoplasm	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000441317	SCV000503618	likely pathogenic	Acute myeloid leukemia	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000419710	SCV000503619	likely pathogenic	Renal cell carcinoma, papillary, 1	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000430407	SCV000503620	likely pathogenic	Malignant melanoma of skin	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000440367	SCV000503621	likely pathogenic	Transitional cell carcinoma of the bladder	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000422278	SCV000503622	likely pathogenic	Ovarian serous cystadenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000432961	SCV000503623	likely pathogenic	Hepatocellular carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000439264	SCV000503624	likely pathogenic	Gastric adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000422078	SCV000503625	likely pathogenic	Adrenal cortex carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000431883	SCV000503626	likely pathogenic	Multiple myeloma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000445249	SCV000503627	likely pathogenic	Malignant neoplasm of body of uterus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000424455	SCV000503628	likely pathogenic	Neoplasm of brain	2016-05-31	no assertion criteria provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000413804	SCV001979371	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000413804	SCV001980093	pathogenic	not provided		no assertion criteria provided	clinical testing