ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.247+3A>C

dbSNP: rs201854371
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000699846 SCV000828575 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-31 criteria provided, single submitter clinical testing This sequence change falls in intron 3 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 individual(s) with Marfan syndrome (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 577165). 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. This variant disrupts the c.247+3 nucleotide in the FBN1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 19293843, 28941062). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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