Submissions for variant NM_000138.5(FBN1):c.3144del (p.Ile1048fs)

dbSNP: rs1555398672

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001381676	SCV001580169	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-12-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile1048Metfs*40) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Marfan syndrome (PMID: 21542060). ClinVar contains an entry for this variant (Variation ID: 549132). For these reasons, this variant has been classified as Pathogenic.
Centre of Medical Genetics, University of Antwerp	RCV000663604	SCV002025565	pathogenic	Marfan syndrome	2021-03-01	criteria provided, single submitter	research	PM2, PVS1, PP1, PP4
Center for Medical Genetics Ghent, University of Ghent	RCV000663604	SCV000786924	likely pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing