ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4210+1G>A

dbSNP: rs730880106
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre of Medical Genetics, University of Antwerp RCV000157233 SCV002025305 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS7, PP4
Labcorp Genetics (formerly Invitae), Labcorp RCV001850180 SCV002228077 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-02-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 34 of the FBN1 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 FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Marfan syndrome (PMID: 25652356, 29357934, 31098894). ClinVar contains an entry for this variant (Variation ID: 180359). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004535021 SCV004107915 pathogenic FBN1-related disorder 2022-12-30 criteria provided, single submitter clinical testing The FBN1 c.4210+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has previously been reported to be causative for Marfan syndrome (Baudhuin et al 2015. PubMed ID: 25652356; Becerra-Muñoz VM et al 2018. PubMed ID: 29357934; Li J et al 2019. PubMed ID: 31098894; Hernándiz A et al 2020. PubMed ID: 33174221; Chen S et al 2021. PubMed ID: 34957211). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in FBN1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Blueprint Genetics RCV000157233 SCV000206960 likely pathogenic Marfan syndrome 2014-08-25 no assertion criteria provided clinical testing
Center for Medical Genetics Ghent, University of Ghent RCV000157233 SCV000787033 pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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