Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001389512 | SCV001590904 | pathogenic | Cobalamin C disease | 2022-04-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MMACHC protein in which other variant(s) (p.Tyr222*) have been determined to be pathogenic (PMID: 16311595, 19767224, 30157807). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1075815). This premature translational stop signal has been observed in individual(s) with methylmalonic aciduria and homocystinuria (PMID: 30157807). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp200*) in the MMACHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the MMACHC protein. |
Baylor Genetics | RCV001389512 | SCV004193168 | pathogenic | Cobalamin C disease | 2023-10-16 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001389512 | SCV002089549 | pathogenic | Cobalamin C disease | 2021-07-30 | no assertion criteria provided | clinical testing |