Submissions for variant NM_001999.4(FBN2):c.4763A>T (p.Asp1588Val)

gnomAD frequency: 0.00009  dbSNP: rs202218356

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002313304	SCV000738974	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-05-11	criteria provided, single submitter	clinical testing	The p.D1588V variant (also known as c.4763A>T), located in coding exon 37 of the FBN2 gene, results from an A to T substitution at nucleotide position 4763. The aspartic acid at codon 1588 is replaced by valine, an amino acid with highly dissimilar properties. This variant was previously reported in the SNPDatabase as rs202218356. Based on data from ExAC, the T allele has an overall frequency less than 0.01% (6/106189). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000696433	SCV000824995	likely benign	Congenital contractural arachnodactyly	2024-01-21	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003144399	SCV003834019	uncertain significance	not provided	2021-08-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003980202	SCV004793881	likely benign	FBN2-related condition	2024-01-29	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).