Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672182 | SCV000797262 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2018-01-18 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000781610 | SCV000919782 | pathogenic | Methylmalonic acidemia | 2018-03-11 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.753+2T>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. c.753+2T>A has been reported in the literature in multiple individuals affected with Methylmalonic Acidemia. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function in a patient with a compound heterozygote genotype of 753+2T>A/2206C>T. The most pronounced variant effect results in a Methylmalonyl-CoA mutase activity with (+AdoCbl, 50 M) and without AdoCbl (-AdoCbl) in crude homogenates of patient fibroblasts of -AdoCbl: 50 (control: 1058 +/- 381) and +AdoCbl: 199 (control: 2569 +/- 782) respectively. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |