Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668034 | SCV000792577 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-07-05 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000760390 | SCV000890261 | pathogenic | not provided | 2019-02-01 | criteria provided, single submitter | clinical testing | The E224X variant has been reported previously in an individual with mut0 MMA who also had a second nonsense variant identified in the MUT gene (Worgan et al., 2006). The E224X variant is not observed in large population cohorts (Lek et al., 2016). This E224X variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret E224X as pathogenic. |
Invitae | RCV000668034 | SCV001223502 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2019-03-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu224*) in the MUT gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with methylmalonic aciduria (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 552718). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). For these reasons, this variant has been classified as Pathogenic. |