ClinVar Miner

Submissions for variant NM_000501.4(ELN):c.1150+1G>A (rs727503030)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626794 SCV000747497 pathogenic Hypertelorism; Abnormality of digit; Venous malformation; Dural ectasia 2017-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000200273 SCV000250044 pathogenic not provided 2015-05-19 criteria provided, single submitter clinical testing The c.1150+1G>A mutation in the ELN gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. This splice site mutation destroys the canonical splice donor site in intron 19. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1150+1G>A mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1150+1G>A as a disease-causing mutation. This variant was found in ELN.
Invitae RCV000150639 SCV000622199 likely pathogenic Supravalvar aortic stenosis 2017-09-06 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 19 of the ELN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs727503030, ExAC 0.009%). This variant has not been reported in the literature in individuals with an ELN-related disease. ClinVar contains an entry for this variant (Variation ID: 163391). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ELN are known to be pathogenic (PMID: 9215670, 11175284). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150639 SCV000197974 pathogenic Supravalvar aortic stenosis 2016-09-21 criteria provided, single submitter clinical testing The c.1150+1G>A variant in ELN has not been reported in the literature but has b een previously identified by our laboratory in 1 individual with mid-thoracic sy ndrome. This variant has been identified in 6/66734 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Please not e that for diseases with clinical variability, reduced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the genera l population. This variant occurs in the invariant region (+/- 1,2) of the splic e consensus sequence and is predicted to cause altered splicing leading to an ab normal or absent protein. Splice-site alterations and other loss-of-function var iants in the ELN gene are established as disease-causing for supravalvular aorti c stenosis (SVAS; Human Gene Mutation Database, HGMD). In summary, this variant meets our criteria to be classified as pathogenic for SVAS in an autosomal domin ant manner based on the predicted impact of the variant.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000660643 SCV000782767 likely pathogenic Cutis laxa, autosomal dominant 1; Supravalvar aortic stenosis 2018-01-26 criteria provided, single submitter clinical testing

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