VHL E70K (c.208G>003eA)

VHL基因的良性错义变异率较低，已知与VHL疾病有明确关联。E70K错义突变位于vhl的β区，在开放源基因组数据库中很少见（exac中的等位基因频率为0.00001489，gnomad中的等位基因频率为4.365e-6），并且在几个有vhl疾病症状的个体中被发现（见证据陈述）。因此，在良性错义变异率较低的基因中，这种变异可被指定为ACMG编码‘pp2’-错义突变，错义变异是常见的疾病机制。虽然该变种在exac和gnomad中登记过一次，但可以应用‘pm2’（在esp、1000个基因组或exac的对照中不存在），因为vhl表现有时在成年后期出现。因此，该等位基因可能在尚未受症状影响的先证者身上检测到。
The VHL gene has a low rate of benign missense variation and is known to be definitively associated with VHL disease. The E70K missense mutation, located in the Beta-domain of VHL, is rare in open-source genome databases (0.00001489 allele frequency in ExAC, 4.365e-6 allele frequency in gnomAD) and was identified in several individuals with VHL disease symptoms (see evidence statements). Thus, this variant could be assigned ACMG code 'PP2' - Missense mutation in a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. Although this variant is registered once in ExAC and gnomAD, 'PM2' could be applied (Absent from controls in ESP, 1000 Genomes or ExAC) because VHL manifestations sometimes emerge later in adulthood. Thus, the allele may have been detected in a proband who was not yet affected by symptoms.