Submissions for variant NM_002755.4(MAP2K1):c.315C>T (p.Pro105=)

gnomAD frequency: 0.00061  dbSNP: rs144166521

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000227559	SCV000616550	benign	RASopathy	2017-05-09	reviewed by expert panel	curation	The filtering allele frequency of the c.315C>T (p.Pro105=) variant in the MAP2K1 gene is 0.01% (64/66728) of European 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	RCV000037594	SCV000061252	likely benign	not specified	2016-11-23	criteria provided, single submitter	clinical testing	p.Pro105Pro in exon 3 in MAP2K1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and it is not locate d within the splice consensus sequence. It has been identified in 0.1% (64/66728 ) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs144166521).
GeneDx	RCV000037594	SCV000170177	benign	not specified	2013-08-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000227559	SCV000287686	benign	RASopathy	2024-01-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000037594	SCV000309174	likely benign	not specified		criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813323	SCV002060558	benign	Noonan syndrome and Noonan-related syndrome	2021-04-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321510	SCV002610170	likely benign	Cardiovascular phenotype	2022-02-21	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	RCV001729364	SCV004132712	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	MAP2K1: BP4, BP7
Clinical Genetics, Academic Medical Center	RCV000037594	SCV001978752	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729364	SCV001980017	likely benign	not provided		no assertion criteria provided	clinical testing