Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002037976 | SCV002237066 | pathogenic | Cobalamin C disease | 2020-12-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp207Metfs*3) in the MMACHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the MMACHC protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MMACHC protein. Other variant(s) that disrupt this region (p.Tyr222*) have been determined to be pathogenic (PMID: 16311595, 19767224, 30157807). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with MMACHC-related conditions. |