Submissions for variant NM_000138.5(FBN1):c.6834C>T (p.Pro2278=)

gnomAD frequency: 0.00006  dbSNP: rs397515839

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035255	SCV000058902	likely benign	not specified	2011-12-30	criteria provided, single submitter	clinical testing	Pro2278Pro variant in exon 55 of FBN1: This variant is not expected to have clin ical significance because it does not alter an amino acid residue, is not locate d within the splice consensus sequence, and it has been identified in 0.014% (1/ 7020) of European American chromosomes by the NHBLI Exome sequencing project in a clinical cohort that included individuals with heart disease (http://evs.gs.wa shington.edu/EVS, rs148250409).
GeneDx	RCV001703453	SCV000516736	likely benign	not provided	2021-02-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000470181	SCV000557022	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000769625	SCV000738800	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-10-20	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769625	SCV000901022	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-08-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769625	SCV000904641	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-07-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035255	SCV003800651	benign	not specified	2023-01-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996192	SCV004822426	likely benign	Marfan syndrome	2024-02-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528167	SCV000302581	likely benign	FBN1-related disorder	2024-01-29	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).