ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3839_3846del (p.Asp1280fs)

dbSNP: rs113603747
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508252 SCV000603652 pathogenic not specified 2016-12-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002358391 SCV002621667 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2022-03-21 criteria provided, single submitter clinical testing The c.3839_3846delATGTCAAT pathogenic mutation, located in coding exon 31 of the FBN1 gene, results from a deletion of 8 nucleotides at nucleotide positions 3839 to 3846, causing a translational frameshift with a predicted alternate stop codon (p.D1280Gfs*3). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with FBN1-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV002527352 SCV003238395 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-09-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as 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: 439711). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp1280Glyfs*3) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843).

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