ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.510C>G (p.Tyr170Ter)

dbSNP: rs111671429
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029747 SCV000052400 likely pathogenic Marfan syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
GeneDx RCV000492866 SCV000582575 pathogenic not provided 2015-09-09 criteria provided, single submitter clinical testing The Y170X nonsense variant has been reported in one individual with skeletal findings associated with Marfan syndrome, a dilated aorta, mitral valve prolapse, and lumbosacral dural ectasia (Biggin et al., 2004). Y170X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the FBN1 gene have been reported in HGMD in association with Marfan syndrome (Stenson et al., 2014). Furthermore, the Y170X variant 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. In summary, Y170X in the FBN1 gene is interpreted as a pathogenic variant.
Invitae RCV001221819 SCV001393882 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-07-12 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 36085). This premature translational stop signal has been observed in individuals with Marfan syndrome or thoracic aortic aneurysm and dissection (PMID: 14695540, 21360310). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr170*) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital RCV000492866 SCV001449698 pathogenic not provided 2017-08-14 criteria provided, single submitter clinical testing
DASA RCV000029747 SCV002588794 pathogenic Marfan syndrome 2022-11-03 criteria provided, single submitter clinical testing The c.510C>G;p.(Tyr170*) variant creates a premature translational stop signal in the FBN1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID:36085; PMID: 14695540; 21360310; 16342915; 31730815) - PS4. This variant is not present in population databases (rs111671429, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic.
Center for Medical Genetics Ghent, University of Ghent RCV000029747 SCV000787111 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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