Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666211 | SCV000790466 | likely pathogenic | Methylmalonic aciduria, cblB type | 2017-03-21 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000666211 | SCV001208978 | pathogenic | Methylmalonic aciduria, cblB type | 2022-05-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 551214). This premature translational stop signal has been observed in individual(s) with methylmalonic aciduria due to cobalamin B deficiency (PMID: 17410422). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu152*) in the MMAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MMAB are known to be pathogenic (PMID: 15781192, 16410054). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194231 | SCV001363599 | likely pathogenic | Methylmalonic acidemia | 2019-02-21 | criteria provided, single submitter | clinical testing | Variant summary: MMAB c.454G>T (p.Glu152X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.700C>T/p.Gln234X). The variant was absent in 148518 control chromosomes. c.454G>T has been reported in the literature in individuals affected with Methylmalonic Acidemia (Vatanavicharn_2012). These data indicate that the variant may be associated with disease. One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000666211 | SCV004193138 | pathogenic | Methylmalonic aciduria, cblB type | 2023-10-04 | criteria provided, single submitter | clinical testing |