Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Human Genome Sequencing Center Clinical Lab, |
RCV001171634 | SCV000999933 | pathogenic | Intellectual disability | 2019-11-18 | criteria provided, single submitter | research | The c.263G>A (p.Trp88Ter) variant in the MED13L gene is predicted to introduce a premature translation termination codon. It is predicted to cause loss of normal protein function either through abnormal, prematurely truncated protein, or by absence of protein product due to nonsense-mediated mRNA decay. This variant was not observed in the general population (gnomAD database). Multiple studies, reviewed in Asadollahi et al. 2017 (PMID: 28645799), have reported on the role of loss of function variants in the MED13L gene in individuals with intellectual disability with or without heart defects. This variant was identified in an adult undergoing exome sequencing due to a history of intellectual disability and developmental delay. For these reasons, this variant has been classified as Pathogenic. |
Labcorp Genetics |
RCV001047664 | SCV001211635 | pathogenic | Transposition of the great arteries, dextro-looped | 2019-11-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MED13L are known to be pathogenic (PMID: 23403903). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MED13L-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp88*) in the MED13L gene. It is expected to result in an absent or disrupted protein product. |