Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002317557 | SCV000851043 | likely pathogenic | Inborn genetic diseases | 2017-06-12 | criteria provided, single submitter | clinical testing | The c.401_402+2delGTGT variant results from a deletion of 4 nucleotides located at positions 401 to 402 as well as the first 2 intronic nucleotides after coding exon 3 of the MEF2C gene, deleting the canonical donor splice site. These nucleotide positions are highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice donor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). As such, this variant is classified as likely pathogenic. |
| Invitae | RCV003619718 | SCV004411251 | pathogenic | Intellectual disability, autosomal dominant 20 | 2022-11-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys134Leufs*52) in the MEF2C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEF2C are known to be pathogenic (PMID: 20513142). This variant has not been reported in the literature in individuals affected with MEF2C-related conditions. 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: 589844). This variant is also known as c.401_402+2del. |