ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5225-3C>A

dbSNP: rs876657810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000213111 SCV000271781 uncertain significance not specified 2015-01-08 criteria provided, single submitter clinical testing The c.5225-3C>A variant in FBN1 has not been previously reported in individuals with Marfan syndrome or in large population studies. This variant is located in the 3' splice region. Computational tools do not suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. I n summary, the clinical significance of the c.5225-3C>A variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001305947 SCV001495301 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-03-04 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with clinical features of Marfan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 228685). This sequence change falls in intron 42 of the FBN1 gene. It does not directly change the encoded amino acid sequence of the FBN1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001582735 SCV001812207 uncertain significance not provided 2021-05-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on splicing; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 228685; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 9536098, 17576681)

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