Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Foundation for Research in Genetics and Endocrinology, |
RCV001260224 | SCV001435289 | likely pathogenic | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2020-08-24 | criteria provided, single submitter | clinical testing | A heterozygous missense variation in exon 3 of the MTHFR gene that results in the amino acid substitution of Glycine for Aspartic acid at codon 159 was detected. The observed variant c.476A>G (p.Asp159Gly) lies in the methylenetetrahydrofolate reductase domain of the MTHFR protein and has previously been reported at a nearby position (c.474A>T; p.G158G) in a homozygous state, in patients affected with homocystinuria (Ben-Shachar et al. 2012). The variant has not been reported in the 1000 genomes and gnomAD databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic. |