This assay detects only the C677T and A1298C mutations in the MTHFR gene. The most well-studied polymorphism related to neural tube defects changes a single DNA building block (nucleotide) in the MTHFR gene. Specifically, it replaces the nucleotide cytosine with the nucleotide thymine at position 677 (written as 677C>T). This common variant results in a form of methylenetetrahydrofolate reductase that has reduced activity at higher temperatures (thermolabile). People with the 677C>T polymorphism, particularly those with two copies of the genetic change, have elevated levels of homocysteine in their blood resulting from the reduced activity of methylenetetrahydrofolate reductase. Research indicates that individuals who have the 677C>T polymorphism on both copies of the MTHFR gene have an increased risk of developing vascular disease, including heart disease and stroke. The 677C>T polymorphism has also been suggested as a risk factor for cleft lip and palate.