Submissions for variant NM_000138.5(FBN1):c.5442C>T (p.Asn1814=)

gnomAD frequency: 0.00004  dbSNP: rs397515822

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035226	SCV000058871	likely benign	not specified	2008-03-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397998	SCV000392296	likely benign	Weill-Marchesani syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000303570	SCV000392297	likely benign	Geleophysic dysplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000355990	SCV000392298	likely benign	Acromicric dysplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000263353	SCV000392299	likely benign	Ectopia lentis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297465	SCV000392300	likely benign	Marfan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000354690	SCV000392301	likely benign	MASS syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000276436	SCV000392302	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000330003	SCV000392303	likely benign	Stiff skin syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000589101	SCV000520906	likely benign	not provided	2021-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589101	SCV000695559	benign	not provided	2016-05-02	criteria provided, single submitter	clinical testing	Variant summary: The c.5442C>T (p.Asn1814=) in FBN1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 in silico programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00014 (18/121254 chrs tested), which exceeds the maximal expected frequency of a pathogenic allele (0.000125) in this gene. The variant of interest was cited as Likely Benign by reputable database/clinical laboratory. Taking together, the variant was classified as Benign.
Color Diagnostics, LLC DBA Color Health	RCV000276436	SCV000913674	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-07-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001468352	SCV001672395	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-01-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000276436	SCV002041998	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2020-03-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000276436	SCV002652267	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-12-27	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.
All of Us Research Program, National Institutes of Health	RCV000297465	SCV004814658	likely benign	Marfan syndrome	2024-01-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004737172	SCV005353148	likely benign	FBN1-related disorder	2024-07-10	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).