Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489927 | SCV000576917 | pathogenic | not provided | 2017-04-14 | criteria provided, single submitter | clinical testing | The R152X nonsense variant in the MUT gene has been reported previously in association with methylmalonic acidemia. (MartÃnez et al., 2005; Dündar et al., 2012; Sawangareetrakul et al., 2015). The R152X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret R152X to be a pathogenic variant. |
Invitae | RCV000489927 | SCV000833732 | pathogenic | not provided | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg152*) 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 (rs780068818, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with methylmalonic acidemia (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 426467). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192658 | SCV001360917 | pathogenic | Methylmalonic acidemia | 2019-07-19 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.454C>T (p.Arg152X) 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 allele was found at a frequency of 2.4e-05 in 245204 control chromosomes (gnomAD). The variant, c.454C>T, has been reported in the literature in multiple individuals affected with Methylmalonic Acidemia (Martinez_2005, Wogan_2006, Liu_2012). These data indicate that the variant is very likely to be associated with disease. One publication, Liu_2012, reports that variant effect results in <10% of normal activity. Three ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Fulgent Genetics, |
RCV000667884 | SCV002794419 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2022-02-05 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000667884 | SCV000792396 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-06-27 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001271720 | SCV001453068 | pathogenic | Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |