Submissions for variant NM_000138.5(FBN1):c.2187A>C (p.Leu729=)

gnomAD frequency: 0.00026  dbSNP: rs61730055

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001703561	SCV000516759	likely benign	not provided	2021-01-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464891	SCV000557067	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-01-16	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000430847	SCV000710905	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Leu729Leu in Exon 18 of FBN1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.1% (10/10384) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs61730055).
Ambry Genetics	RCV001180310	SCV000738828	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-05-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV001180310	SCV001345209	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-11-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996028	SCV004814912	likely benign	Marfan syndrome	2023-12-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530561	SCV004727679	likely benign	FBN1-related disorder	2023-01-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).