ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1098G>T (p.Trp366Cys)

dbSNP: rs1555400595
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001387166 SCV001587726 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-01-15 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 366 of the FBN1 protein (p.Trp366Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Marfan syndrome (PMID: 11700157, 28855619; Invitae). ClinVar contains an entry for this variant (Variation ID: 549004). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. This variant disrupts the p.Trp366 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (PMID: 24161884, 29357934), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Centre of Medical Genetics, University of Antwerp RCV000663442 SCV002025422 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS1, PP4
Center for Medical Genetics Ghent, University of Ghent RCV000663442 SCV000786733 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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