ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7788C>A (p.Tyr2596Ter)

dbSNP: rs1555394142
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000611011 SCV002669047 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2020-01-03 criteria provided, single submitter clinical testing The p.Y2596* pathogenic mutation (also known as c.7788C>A), located in coding exon 62 of the FBN1 gene, results from a C to A substitution at nucleotide position 7788. This changes the amino acid from a tyrosine to a stop codon within coding exon 62. This variant has been detected in an individual with aortic aneurysm (Weerakkody R et al. Genet. Med., 2018 11;20:1414-1422). 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.
Invitae RCV003767738 SCV004574112 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-11-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr2596*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of FBN1-related conditions (PMID: 29543232). ClinVar contains an entry for this variant (Variation ID: 517133). 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.
Centre for Genomic and Experimental Medicine, University of Edinburgh RCV000611011 SCV000731240 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection no assertion criteria provided research

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