ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.52C>T (p.Gln18Ter) (rs121918248)

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Total submissions: 5
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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 2019-12-22 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. This variant is present in population databases (rs121918248, ExAC 0.003%). This variant has been observed in individual(s) with methylmalonic aciduria (PMID: 16281286, 1970180). 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 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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
GeneReviews RCV000203362 SCV000258490 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2016-12-01 no assertion criteria provided literature only mut(0) enzymatic subtype when homozygous

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