Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000788660 | SCV000927850 | uncertain significance | not provided | 2018-08-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000788660 | SCV002032798 | uncertain significance | not provided | 2023-01-27 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Canonical splice site variant with an unclear effect on protein function |
Invitae | RCV003517266 | SCV004329405 | uncertain significance | Supravalvar aortic stenosis | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 20 of the ELN 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 ELN are known to be pathogenic (PMID: 11175284). This variant is present in population databases (rs782568267, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ELN-related conditions. ClinVar contains an entry for this variant (Variation ID: 636745). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |