Submissions for variant NM_000138.5(FBN1):c.8268G>A (p.Trp2756Ter)

dbSNP: rs267606796

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851898	SCV002236718	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp2756*) in the FBN1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 116 amino acid(s) of the FBN1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Marfan syndrome (PMID: 1631074). This variant is also known as a G-to-A transition at nucleotide 5574. ClinVar contains an entry for this variant (Variation ID: 16424). This variant disrupts a region of the FBN1 protein in which other variant(s) (p.Leu2854Profs*9) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000017886	SCV000038165	pathogenic	Marfan syndrome	1992-07-01	no assertion criteria provided	literature only