Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588466 | SCV000695570 | likely pathogenic | Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections | 2016-05-10 | criteria provided, single submitter | clinical testing | Variant summary: The FBN1 c.5874C>A (p.Cys1958*) variant results in a premature termination codon and predicted to cause a truncated or absent FBN1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 121166 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor was evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as Likely Pathogenic. |
ARUP Laboratories, |
RCV001002491 | SCV001160444 | pathogenic | not specified | 2019-03-29 | criteria provided, single submitter | clinical testing | The FBN1 c.5874C>A; p.Cys1958Ter variant, to our knowledge, has not been described in the medical literature but contains an entry in ClinVar (Variation ID: 495630). It is absent from general population databases (Exome Variant Server and 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 association with Marfan syndrome and are considered pathogenic (Stheneur 2009). Based on available information, the p.Cys1958Ter variant is considered pathogenic. REFERENCES Stheneur C et al. Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene. Eur J Hum Genet. 2009 Sep;17(9):1121-8. |
Invitae | RCV001390032 | SCV001591602 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-07-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 495630). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys1958*) 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). |