Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001008757 | SCV001168541 | likely pathogenic | not provided | 2021-03-05 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 76 amino acids are replaced with 37 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26825575, 26270766, 31589614) |
Invitae | RCV000668405 | SCV001220431 | pathogenic | Cobalamin C disease | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp207Glyfs*38) 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 present in population databases (rs765913293, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with cobalamin C deficiency (PMID: 26270766). ClinVar contains an entry for this variant (Variation ID: 553035). 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. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV000668405 | SCV002060297 | likely pathogenic | Cobalamin C disease | 2021-11-18 | criteria provided, single submitter | clinical testing | NM_015506.2(MMACHC):c.619dupG(D207Gfs*38) is a frameshifting truncation variant classified as likely pathogenic in the context of methylmalonic aciduria and homocystinuria, cblC type. D207Gfs*38 has been observed in cases with relevant disease (PMID: 26825575). Functional assessments of this variant are not available in the literature. D207Gfs*38 has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, NM_015506.2(MMACHC):c.619dupG(D207Gfs*38) is a frameshifting truncation variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV000668405 | SCV002816302 | pathogenic | Cobalamin C disease | 2021-12-09 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000668405 | SCV004178212 | likely pathogenic | Cobalamin C disease | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000668405 | SCV004193160 | pathogenic | Cobalamin C disease | 2023-10-26 | criteria provided, single submitter | clinical testing |