Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000167600 | SCV005205321 | likely pathogenic | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2024-06-04 | criteria provided, single submitter | clinical testing | Variant summary: MTHFR c.677_679delTCA (p.Ile226del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant was absent in 251488 control chromosomes. c.677_679delTCA has been reported in the literature in at-least one individual affected with Homocystinuria Due To Methylene Tetrahydrofolate Reductase Deficiency (Burda_2015). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 1.7% of normal activity in the cell line from a patient carrying both the current variant and a pathogenic splice variant resulting in a null allele (Burda_2015). The following publication has been ascertained in the context of this evaluation (PMID: 25736335). ClinVar contains an entry for this variant (Variation ID: 187880). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
University Children's Hospital, |
RCV000167600 | SCV000218481 | pathogenic | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | no assertion criteria provided | clinical testing |