Clinical Domain Working Groups

The ClinGen RASopathy Expert Panel aims to provide high quality, standardized curation of RASopathy gene variants.

Using the recently released ACMG standards and guidelines for the interpretations of sequence variants as our foundation, we refined classification criteria to specifically apply to BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, SOS1, and SOS2 relative to their pathogenicity and mechanism, and considering their allele frequency compared to the incidence of these Noonan syndrome spectrum disorders.

The RASopathy Expert Panel aims to systematically aid in resolution of variant classification differences in ClinVar and provide further curation of the genes involved in the RASopathies.