Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003086756 | SCV003482140 | uncertain significance | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 437 of the MTHFR protein (p.Leu437His). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MTHFR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |