Submissions for variant NM_001999.4(FBN2):c.2042G>A (p.Arg681His)

gnomAD frequency: 0.00001  dbSNP: rs548605398

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198562	SCV000250165	benign	not specified	2018-01-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000227040	SCV000287251	benign	Congenital contractural arachnodactyly	2023-11-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000198562	SCV000308595	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310783	SCV000317343	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2021-11-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000227040	SCV000452633	benign	Congenital contractural arachnodactyly	2018-01-13	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812193	SCV001473102	likely benign	not provided	2020-07-24	criteria provided, single submitter	clinical testing