ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.247+2dup

dbSNP: rs397515772
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Total submissions: 1
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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 RCV000035142 SCV000058783 likely pathogenic Marfan syndrome 2020-10-08 criteria provided, single submitter clinical testing The c.247+2dup variant in FBN1 has been previously reported in two individuals with clinical features of Marfan syndrome and segregated with disease in one affected relative (Stheneur 2009 PMID: 19293843, LMM unpublished data). In one of these individuals, the variant was reportedly a de novo occurrence Stheneur 2009 PMID: PMID: 19293843). This variant was absent from large population databases. This variant is a duplication of the thymine (T) at nucleotide position c.247+2 and is predicted to disrupt the canonical splice site (+/- 1,2), leading to an abnormal or absent protein. Loss of function of the FBN1 gene is an established disease mechanism in autosomal dominant Marfan syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Marfan syndrome. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM6, PS4_Supporting.

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