Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586630 | SCV000696296 | pathogenic | Methylmalonic acidemia | 2016-10-24 | criteria provided, single submitter | clinical testing | Variant summary: The MUT c.1083+2T>A variant involves the alteration of the GT donor splice site of intron 5, which 5/5 splice prediction tools predict abrogation of the donor site. This variant was found in 1/119390 control chromosomes at a frequency of 0.0000084, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUT variant (0.0024152). This variant has been reported in one patient with Methylmalonic Acidemia who was compound heterozygous with another variant c.1328dupT. Taken together, this variant is classified as Pathogenic. |
Invitae | RCV003558446 | SCV004293688 | pathogenic | not provided | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 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). This variant is present in population databases (rs746085723, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with methylmalonic acidemia (PMID: 16281286). ClinVar contains an entry for this variant (Variation ID: 495775). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |