Further, as SDHB is a known tumor suppressor and hence requires inactivation of both alleles for tumorigenesis, the timeframe between SDHB germline (first hit) and somatic loss of the normal SDHB allele (second hit) provides a means by which the SDHAF3 c.157 T > C allele could act. Here, SDHAF3 is linked to neoplasm.