Submissions for variant NM_001999.4(FBN2):c.518C>T (p.Thr173Ile)

dbSNP: rs147157552

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724479	SCV000230187	uncertain significance	not provided	2014-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000724479	SCV000250094	likely benign	not provided	2021-03-16	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000199324	SCV000271786	uncertain significance	not specified	2015-10-30	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Thr173Ile var iant in FBN2 has not been previously reported in individuals with connective tis sue disorders. It has been identified in 0.2% (146/65724) of European chromosom es, including 1 homozygous individual, by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org; dbSNP rs147157552). Computational prediction t ools and conservation analysis suggest that this variant may not impact the prot ein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Thr173Ile variant is uncer tain, its frequency and lack of conservation suggests that it is more likely to be benign.
Invitae	RCV000229340	SCV000287266	likely benign	Congenital contractural arachnodactyly	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000143896	SCV000317367	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-11-29	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.
Illumina Laboratory Services, Illumina	RCV000229340	SCV000452654	benign	Congenital contractural arachnodactyly	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659593	SCV000781432	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000724479	SCV002049528	likely benign	not provided	2021-09-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277283	SCV002565929	likely benign	Ehlers-Danlos syndrome	2020-07-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000659593	SCV002566585	likely benign	Connective tissue disorder	2022-06-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724479	SCV004161350	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	FBN2: BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000199324	SCV004223375	likely benign	not specified	2023-11-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003935229	SCV004748515	likely benign	FBN2-related disorder	2019-04-01	criteria provided, single submitter	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).
Blueprint Genetics	RCV000143896	SCV000188765	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2014-05-19	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000724479	SCV001797510	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000724479	SCV001809024	likely benign	not provided		no assertion criteria provided	clinical testing