Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587349 | SCV000695455 | likely pathogenic | Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections | 2020-10-05 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.1459G>T (p.Glu487X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251122 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1459G>T in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
ARUP Laboratories, |
RCV001811087 | SCV002049640 | pathogenic | not provided | 2021-10-28 | criteria provided, single submitter | clinical testing | The FBN1 c.1459G>T; p.Glu487Ter variant (rs1555400374), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 495556). This variant is also absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with Marfan syndrome and are considered pathogenic (Takeda 2018). Based on available information, this variant is considered to be pathogenic. References: Takeda N et al. Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome. Circ Genom Precis Med. 2018 Jun;11(6):e002058. PMID: 29848614. |