Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029747 | SCV000052400 | likely pathogenic | Marfan syndrome | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Gene |
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, |
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, |
RCV000029747 | SCV000787111 | likely pathogenic | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |