ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1287C>G (p.Tyr429Ter)

gnomAD frequency: 0.00001  dbSNP: rs1346775255
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669883 SCV000794679 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-10-11 criteria provided, single submitter clinical testing
Invitae RCV001376628 SCV001229452 pathogenic not provided 2023-05-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr429*) 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 (no rsID available, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with cobalamin nonresponsive methylmalonic acidemia (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 554278). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282308 SCV002570548 pathogenic Methylmalonic acidemia 2022-07-25 criteria provided, single submitter clinical testing Variant summary: MUT c.1287C>G (p.Tyr429X) 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 251238 control chromosomes. c.1287C>G has been reported in the literature in individuals affected with Methylmalonic Acidemia (eg. Worgan_2006, Chu_2016). 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. Based on the evidence outlined above, the variant was classified as pathogenic.
Natera, Inc. RCV001830442 SCV002077377 pathogenic Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency 2020-09-10 no assertion criteria provided clinical testing

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