We seriously considered chronic lyme as a possibility and even got testing. The test came back negative, although there can be false negatives. We ultimately ruled it out on the basis of certain key symptoms being absent. Basically, we considered a LOT of things and did our best to rank the changes of each illness that might explain the symptoms. We were open to the idea of more than one cause but considered it a remote possibility; fortunately we were right.
Anyhow, homozygous MTHFR C677T can be serious, especially if there are other complicating mutations. Compared to some people my wife has a moderate problem. She had chronic fatigue (not to be necessarily confused with CFIDS), brain fog, autoimmune disease, gluten intolerance, weight gain, pale skin, hairloss, and many more symptoms. But she never lost feeling in her limbs; some people do. When you mess up the methylation cycle, all sorts of things can go wrong.
I'm not sure why you (an anonymous coward, so why am I feeding the trolls?) think that this mutation is of "dubious clinical significance." It's one of the more serious mutations, and the appropriate treatments have worked. Taking methylfolate, a few different forms of B12, and several other supplements has caused massive improvement in energy, return of proper skin tone, hair regrowth, appropriate weight loss, and so on. In other words THE TREATMENT WORKED.
This is one of those fortunate cases where a hard-to-find single cause has been identified. It explains ALL of the symptoms (many of which are secondary, caused by a deficiency caused by the underlying problem), and the treatment has worked very well. It's a little hard to get the exact dosages of vitamins right, because as soon as you get enough of one thing, the body will start repairing things, which requires other chemicals, and cause a deficiency in another thing, etc. So the fix isn't an over-night sort of thing but the progress is rapid.
And my biggest complaint is not that the MDs didn't know how to diagnose this. My complaint is that they EXPLICITLY REFUSED to help us when we were trying to track down the cause. Seriously. Most doctors just didn't have a clue and were unwilling to "do a lot of speculative testing," while some out-right said they refused to help us. Even if we came in with a list of tests to do to try to narrow down a range of possibilities (like a decision tree), they wouldn't do it. We had to figure this out completely on our own.
I don't expect MDs to know everything or be super-human. But I do expect them to listen and take patients seriously.