Submissions for variant NM_002755.4(MAP2K1):c.1137C>T (p.Ile379=)

gnomAD frequency: 0.00103  dbSNP: rs150841154

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000477005	SCV000616560	benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The filtering allele frequency of the c.1137C>T (p.Ile379=) variant in the MAP2K1 gene is 0.175% (26/10406) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037589	SCV000061247	benign	not specified	2012-07-26	criteria provided, single submitter	clinical testing	Ile379Ile in Exon 11 of MEK1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.3% (12/3738) of Afric an American chromosomes from a broad population by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS; dbSNP rs150841154).
PreventionGenetics, part of Exact Sciences	RCV003891459	SCV000309171	benign	MAP2K1-related condition	2019-12-17	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Invitae	RCV000477005	SCV000556851	benign	RASopathy	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001536453	SCV001753212	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813309	SCV002060554	likely benign	Noonan syndrome and Noonan-related syndrome	2017-12-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321500	SCV002607202	likely benign	Cardiovascular phenotype	2022-03-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV001536453	SCV004132715	benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	MAP2K1: BS1, BS2