In a study of 138 unrelated VHL families, 109 germline mutations were found. Missense mutations were more frequently found in families with pheochromocytoma (PC). Deletions. Nonsense, and frameshift mutations were more frequently found in families without PC. Large deletions and mutations predicted to cause truncated protein were associated with lower risk of PC. The mutation of c.214delT was referred to in the paper by c.427delT due to a difference in transcript sequence. This deletion mutation was found in a VHL family without PC (family ID 112). Only moderate evidence for pathogenicity because protein length changes as a result of in-frame deletion in a nonrepeat region or stop-loss variant (ACMG code: PM4).

Germline mutational data on VHL was gathered from various countries to assess variation in germline mutations that produce disease within different populations. Families were grouped according to three possible outcomes of disease: renal cell carcinoma without pheochromocytoma, renal cell carcinoma with pheochromocytoma, or pheochromocytoma alone. SSCP and denaturing gradient gel electrophoresis identified mutations in 300/469 (63%) of families affected with VHL. This germline familial VHL mutation (S72Pfs*87 (c.214delT)) was taken from the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 112CA. It was reported in the paper as c.427delT due to a difference in transcript reference. As reported in Table 3, this mutation is found in VHL family without pheochromocytoma, and with renal cell carcinoma.