ClinVar

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The His1419Arg variant has not been reported in the literature nor previously identified by our laboratory. This variant has also not been identified in large European America n and African American populations by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS), which increases the likelihood that the variant is pathogenic. However, it may be present in other populations. The change to argin ine (Arg) was predicted to be pathogenic using a computational tool clinically v alidated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). Other computational analyses (biochemica l amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong s upport for or against an impact to the protein. In summary, this data is consist ent with a pathogenic role but is insufficient to establish this with certainty.