Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000150634 | SCV000197969 | uncertain significance | not specified | 2011-03-08 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The 469+5G>C va riant in ELN has not been reported in the literature nor previously been identif ied by our laboratory. This variant is located in the 5' splice region, but does not affect the invariant +1 and +2 positions. However, positions +3 to +6 are p art of the splicing consensus sequence and variants involving these positions so metimes affect splicing. Four computational tools (SpliceSiteFinder-like, MaxEnt Scan, NNSPLICE, GeneSplicer) predict that this variant affects splicing but thes e tools have not been sufficiently validated to assume pathogenicity. However, s plice-site alterations in the ELN gene are a reported cause of SVAS (Human Genom e Mutation Database, HGMD), which increases the likelihood that the 469+5G>C var iant is pathogenic. In summary, the available data are so far consistent with a pathogenic role but additional studies (family and control studies) are needed t o determine the clinical significance of this variant with certainty. |
| Invitae | RCV003764912 | SCV004682166 | uncertain significance | Supravalvar aortic stenosis | 2023-05-23 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: 163384). This variant has been observed in individual(s) with supravalvar aortic stenosis (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 of the ELN gene. It does not directly change the encoded amino acid sequence of the ELN protein. It affects a nucleotide within the consensus splice site. |