Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000078448 | SCV000227075 | pathogenic | not provided | 2013-02-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000078448 | SCV000490626 | pathogenic | not provided | 2023-09-19 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34930662, 35361390, 16281286, 25525159, 25959030, 16435223, 17410422, 31998365, 32754920, 33820958, 34668645, 27167370, 31622506, 36186952) |
Counsyl | RCV000175566 | SCV000795253 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-11-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781612 | SCV000919784 | pathogenic | Methylmalonic acidemia | 2018-05-07 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.91C>T (p.Arg31X) 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 (e.g., p.Gly284X and p.Arg467X). The variant allele was found at a frequency of 1.8e-05 in 276662 control chromosomes. This frequency is not higher than expected for a pathogenic variant in MUT causing Methylmalonic Acidemia (1.8e-05 vs 0.0024), allowing no conclusion about variant significance. c.91C>T has been reported in the literature in multiple individuals affected with Methylmalonic Acidemia as both a homozygous and compound heterozygous allele. These data indicate that the variant is very likely to be associated with disease. One publication reports experimental evidence showing a significant reduction in the propionate incorporation compared to controls (Worgan_2006), suggesting that the methylmalonyl-CoA mutase enzyme is impaired or absent. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Hudson |
RCV000175566 | SCV000993428 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2019-02-07 | criteria provided, single submitter | research | ACMG codes: PVS1, PS3, PM2, PP5 |
Invitae | RCV000078448 | SCV001383404 | pathogenic | not provided | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg31*) 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 (rs398123278, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency (PMID: 16281286, 16435223, 17410422). ClinVar contains an entry for this variant (Variation ID: 92688). For these reasons, this variant has been classified as Pathogenic. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251962 | SCV002523606 | pathogenic | See cases | 2019-05-15 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1, PM2, PP5 |
Fulgent Genetics, |
RCV000175566 | SCV002792729 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2022-01-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000175566 | SCV000258491 | not provided | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | no assertion provided | literature only | mut(0) enzymatic subtype when homozygous | |
Natera, |
RCV001826711 | SCV002075448 | pathogenic | Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency | 2020-08-04 | no assertion criteria provided | clinical testing |