ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1946del (p.Pro649fs) (rs1554158754)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672834 SCV000797980 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-02-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199896 SCV001370652 likely pathogenic Methylmalonic acidemia 2020-05-07 criteria provided, single submitter clinical testing Variant summary: MUT c.1946delC (p.Pro649LeufsX23) 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 251376 control chromosomes. c.1946delC has been reported in the literature in at least one individual affected with Methylmalonic Acidemia (e.g. Worgan_2006). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001386489 SCV001586732 pathogenic not provided 2020-03-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro649Leufs*23) in the MUT gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with methylmalonic acidemia (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 556782). Loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). For these reasons, this variant has been classified as Pathogenic.

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