ClinVar Miner

Submissions for variant NM_000255.3(MMUT):c.1084-10A>G (rs777031588)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000642162 SCV000800784 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-08-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000732448 SCV000860408 pathogenic not provided 2018-03-16 criteria provided, single submitter clinical testing
GeneDx RCV000186045 SCV000239009 uncertain significance not specified 2016-10-06 criteria provided, single submitter clinical testing The c.1084-10 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1084-10 A>G sequence change has been reported previously in two patients with methylmalonic acidemia (Liu et al., 2012). Using an in-silico splice prediction model, the authors predict that c.1084-10 A>G creates a cryptic splice site; however, no functional studies were performed to determine the true effect of c.1084-10 A>G on splicing in vivo (Liu et al., 2012). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000642162 SCV000763816 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-02-09 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the MUT gene. It does not directly change the encoded amino acid sequence of the MUT protein. This variant is present in population databases (rs777031588, ExAC 0.03%). This variant has been reported in combination with another MUT variant in individuals affected with methylmalonic aciduria (PMID: 23430940, Invitae). ClinVar contains an entry for this variant (Variation ID: 203845). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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