ClinVar

Description

A novel L92R variant that is likely pathogenic was identified in the MAP2K1 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It has, however, been observed to be inherited in an apparently de novo manner in two patients tested at GeneDx. The variant 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. L92R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species; however, in in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.