Sometime in the 15th century a viable mutation appeared in the human genome.

Among the primitive hunters and gatherers a mutation has appeared that seems to be spreading rapidly.

Occasionally an odd mutation in that direction would appear but, as you point out, it could never gain a foothold again.

So far, the mutations appeared to have caused no harm.

Few cases have been reported, where disease-causing mutations appear at the high frequencies supported by balanced selection.

Second, mutations can appear later in life and cause cancer, as an oncogene.

The study of fossils, on the other hand, can more specifically pinpoint when and in what organism a mutation first appeared.

Most mutations do not appear to have any selective effect one way or the other on the organism.

A mutation on chromosome 5 appears to be associated with cancer of the colon.

In most cases, such mutations appear to be transmitted as an autosomal dominant trait.