ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7204+3A>G

dbSNP: rs1057518076
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413052 SCV000491463 uncertain significance not provided 2023-06-01 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 (gnomAD); In silico analysis supports that this variant does not alter splicing
Labcorp Genetics (formerly Invitae), Labcorp RCV000462540 SCV000544919 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-02 criteria provided, single submitter clinical testing This sequence change falls in intron 58 of the FBN1 gene. It does not directly change the encoded amino acid sequence of the FBN1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with Marfan syndrome (Invitae; external communication). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372922). Variants that disrupt 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. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002374618 SCV002672365 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-11-22 criteria provided, single submitter clinical testing The c.7204+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 57 in the FBN1 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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