Submissions for variant NM_001999.4(FBN2):c.2801G>A (p.Arg934Gln)

gnomAD frequency: 0.00014  dbSNP: rs376194507

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721271	SCV000250176	uncertain significance	not provided	2023-01-30	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659608	SCV000781447	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000705520	SCV000834520	likely benign	Congenital contractural arachnodactyly	2024-01-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001721271	SCV001961900	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FBN2: BS1
Ambry Genetics	RCV002433877	SCV002748073	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2023-09-05	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.
Revvity Omics, Revvity	RCV001721271	SCV003834017	uncertain significance	not provided	2019-11-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003407699	SCV004115025	uncertain significance	FBN2-related disorder	2023-04-19	criteria provided, single submitter	clinical testing	The FBN2 c.2801G>A variant is predicted to result in the amino acid substitution p.Arg934Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-127686571-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.