Submissions for variant NM_001999.4(FBN2):c.4246A>G (p.Thr1416Ala)

gnomAD frequency: 0.00040  dbSNP: rs200837433

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196474	SCV000250293	uncertain significance	not specified	2016-10-14	criteria provided, single submitter	clinical testing	The T1416A variant in the FBN2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T1416A variant was observed on 0.27% alleles from individuals of Finnish background in the Exome Aggregation Consortium (ExAC) data set. The T1416A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T1416A as a variant of uncertain significance.
Invitae	RCV000465479	SCV000563018	likely benign	Congenital contractural arachnodactyly	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315592	SCV000738941	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-05-06	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	RCV000465479	SCV001315438	benign	Congenital contractural arachnodactyly	2017-09-13	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277535	SCV002565922	likely benign	Ehlers-Danlos syndrome	2022-07-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003430751	SCV004161336	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	FBN2: BS1