ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1025C>A (p.Ser342Ter) (rs770466993)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665393 SCV000789509 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-02-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587657 SCV000696302 pathogenic Methylmalonic acidemia 2017-06-26 criteria provided, single submitter clinical testing Variant summary: The MUT c.1025C>A (p.Ser342X) variant results in a premature termination codon, predicted to cause a truncated or absent MUT protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One truncation downstream of this position has been classified as pathogenic by our laboratory (e.g. c.1399C>T, p.Arg467X). One in silico tool predicts a damaging outcome for this variant. The variant of interest has been found in a large, broad control population, ExAC in 1/121004 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUT variant (0.0024152). This variant was found in methylmalonic acidemia patients in compound heterozigosity with other pathogenic variants such as MUT c.2080C>T, p.Arg694Trp and c.572C>A, p.Ala191Glu (Acquaviva_HumMut_2005, Nizon_Orph J Rare Dis_2013). Taken together, this variant is classified as pathogenic.
Invitae RCV000665393 SCV000940062 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser342*) in the MUT gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs770466993, ExAC 0.002%). This variant has been observed in several individuals affected with MUT-related conditions (PMID: 15643616, 19375370). ClinVar contains an entry for this variant (Variation ID: 495777). 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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