Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669883 | SCV000794679 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-10-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001376628 | SCV001229452 | pathogenic | not provided | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr429*) in the MUT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). This variant is present in population databases (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with cobalamin nonresponsive methylmalonic acidemia (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 554278). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282308 | SCV002570548 | pathogenic | Methylmalonic acidemia | 2022-07-25 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.1287C>G (p.Tyr429X) 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. The variant was absent in 251238 control chromosomes. c.1287C>G has been reported in the literature in individuals affected with Methylmalonic Acidemia (eg. Worgan_2006, Chu_2016). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Natera, |
RCV001830442 | SCV002077377 | pathogenic | Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency | 2020-09-10 | no assertion criteria provided | clinical testing |