Submissions for variant NM_000138.5(FBN1):c.799_805del (p.Gly267fs)

dbSNP: rs1060501100

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen FBN1 Variant Curation Expert Panel, ClinGen	RCV003235220	SCV003933665	likely pathogenic	Marfan syndrome	2023-06-15	reviewed by expert panel	curation	The NM_00138 c.799_805del, is a frameshift variant in FBN1 and is predicted to result in a premature stop codon at position 327. It is expected to cause a shift in the reading frame and likely results in an absent or disrupted protein product (PVS1). This variant was reported a pathogenic once in ClinVar (Variation ID: 406374). This variant is not present in gnomAD v2.1.1 (PM2_sup; https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: PVS1, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000462295	SCV000544962	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2019-12-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly267Leufs*61) 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 not been reported in the literature in individuals with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 406374). Loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). For these reasons, this variant has been classified as Pathogenic.