ClinVar

Description

Variant summary: MAP2K1 c.291+14_291+19delinsTCTCAC alters a nucleotide located at a position not widely known to affect splicing. This variant is a multinucleotide combination of 291+14G>T, 291+15A>C, 291+17T>C, 291+19A>C. Several computational tools predict a significant impact on normal splicing: Three predict the variant creates a cryptic 3' acceptor site. One predict the variant strengthens a cryptic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 1606022 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.291+14_291+19delinsTCTCAC in individuals affected with Cardiofaciocutaneous Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, however each component variant has been classified as likely benign/benign in Clinvar. Based on the evidence outlined above, the variant was classified as uncertain significance.