ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3778G>T (p.Glu1260Ter)

dbSNP: rs1555398283
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000631942 SCV000753045 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2017-08-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1260*) in the FBN1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with with FBN1-related disease (PMID: 10464652, 27611364, Invitae). Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002343214 SCV002620424 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2021-04-07 criteria provided, single submitter clinical testing The p.E1260* pathogenic mutation (also known as c.3778G>T), located in coding exon 30 of the FBN1 gene, results from a G to T substitution at nucleotide position 3778. This changes the amino acid from a glutamic acid to a stop codon within coding exon 30. This alteration has been detected in cohorts with Marfan syndrome and related phenotypes (Yang H et al. Sci Rep. 2016;6:33002; Schrijver I et al. Am J Hum Genet. 2002;71:223-37; Liu WO et al. Genet Test. 1997;1:237-42). In addition to the clinical data presented in the literature, 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.

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