Submissions for variant NM_000138.5(FBN1):c.4061G>A (p.Trp1354Ter)

dbSNP: rs1060501039

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000463734	SCV000544856	pathogenic	Marfan syndrome	2016-07-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 1354 (p.Trp1354*) of the FBN1 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant has been reported in individuals in the Universal Mutation Database (PMID: 12938084 ). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV002461187	SCV002757581	pathogenic	not provided	2022-05-24	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Reported in a review article of FBN1 variants identified in four international databases; no phenotypic data was provided for this variant (Groth et al., 2017); This variant is associated with the following publications: (PMID: 27906200)
Center for Medical Genetics Ghent, University of Ghent	RCV000463734	SCV000787020	likely pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000463734	SCV001192855	likely pathogenic	Marfan syndrome	2016-10-04	no assertion criteria provided	clinical testing