ClinVar

Description

The c.179_193delTGGGAGAACTGAAGG variant in the MAP2K1 gene have been reported previously as pathogenic variant, or as a benign variant, to our knowledge.The variant was observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating they are not common benign variants in these populations. The c.179_193del15 variant is an in-frame deletion of five amino acid residues, denoted p.Val60_Lys64del. These residues spanning p.Val60 to p.Asp66 are conserved across species. A germline point mutation (p.V60G) in this region and other nearby variants (p.K59del, p.D67N) have been reported in the Human Gene Mutation Database in association with CFC syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In addition, multiple similar in-frame deletions in somatic cell tumors in the MAP2K1 gene have been reported in an external variant database in association with lymphoid neoplasms (Forbes et al., 2015). The heterozygous de novo presence of c.179_193del15 is interpreted as likely pathogenic, which may be related to failure to thrive, developmental delay, hypotonia, hemangiomas, and pectus excavatum.