ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6379+1G>A

dbSNP: rs397515833
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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 RCV000035242 SCV000058888 likely pathogenic Marfan syndrome 2011-04-22 criteria provided, single submitter clinical testing This variant 6379+1G>A has not been reported in the literature. However, it is p redicted to cause abnormal splicing because the nucleotide substitution occurs i n a highly conserved splice consensus sequence. A different nucleotide change at the same position (6379+1G>T) has been previously reported in 1 individual with a clinical diagnosis of Marfan syndrome, supporting a pathogenic role for 6379+ 1G>A variant (Attanasio 2008). As such, this variant is likely to be pathogenic.
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000035242 SCV000889970 pathogenic Marfan syndrome 2018-05-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852715 SCV002311124 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-11-04 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 42400). Disruption of this splice site has been observed in individual(s) with Marfan syndrome (PMID: 18435798). This sequence change affects a donor splice site in intron 52 of the FBN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency).

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