Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673042 | SCV000798208 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2018-03-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269118 | SCV001448362 | pathogenic | Methylmalonic acidemia | 2020-11-02 | criteria provided, single submitter | clinical testing | Variant summary: MUT c.1677-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3 acceptor site with three of them also predicting it creates a new cryptic exonic 3acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251050 control chromosomes (gnomAD). c.1677-1G>C has been reported in the literature in multiple individuals affected with Methylmalonic Acidemia (e.g. Acquaviva_2005, Worgan_2006, Forny_2016). These data indicate that the variant is very likely to be associated with disease. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
MGZ Medical Genetics Center | RCV000673042 | SCV002581679 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2022-08-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002531330 | SCV003439421 | pathogenic | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 556968). Disruption of this splice site has been observed in individuals with methylmalonic aciduria (PMID: 15643616). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 9 of the MUT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). |