Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000203362 | SCV000792798 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-07-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001376600 | SCV001228047 | pathogenic | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln18*) 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 (rs121918248, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with methylmalonic aciduria (PMID: 1970180, 16281286). ClinVar contains an entry for this variant (Variation ID: 1877). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001553684 | SCV001774637 | pathogenic | Methylmalonic acidemia | 2021-07-19 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.52C>T (p.Gln18X) 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 250874 control chromosomes. c.52C>T has been reported in the literature in individuals affected with Methylmalonic Acidemia (Ghosh_2017, Worgan_2006). Cell lines with the variant were reported to have no detectable enzymatic activity (Ledley_1990). 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/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000001954 | SCV000022112 | pathogenic | METHYLMALONIC ACIDURIA, mut(0) TYPE | 1987-03-01 | no assertion criteria provided | literature only | |
Gene |
RCV000203362 | SCV000258490 | not provided | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | no assertion provided | literature only | mut(0) enzymatic subtype when homozygous | |
Natera, |
RCV001831507 | SCV002075450 | pathogenic | Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency | 2020-10-27 | no assertion criteria provided | clinical testing |