Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000148299 | SCV001574745 | likely pathogenic | Cobalamin C disease | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change affects codon 92 of the MMACHC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MMACHC protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with MMACHC-related conditions (PMID: 23837176). ClinVar contains an entry for this variant (Variation ID: 161118). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the c.276G nucleotide in the MMACHC gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 20652818, 23837176, 25894566). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV000148299 | SCV004193158 | pathogenic | Cobalamin C disease | 2023-10-30 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000148299 | SCV000195687 | pathogenic | Cobalamin C disease | 2013-08-01 | no assertion criteria provided | literature only |