Submissions for variant NM_000138.5(FBN1):c.2600A>G (p.Asn867Ser)

gnomAD frequency: 0.00004  dbSNP: rs145464311

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001176306	SCV000738938	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2017-12-16	criteria provided, single submitter	clinical testing	The p.N867S variant (also known as c.2600A>G), located in coding exon 21 of the FBN1 gene, results from an A to G substitution at nucleotide position 2600. The asparagine at codon 867 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000763968	SCV000894919	uncertain significance	Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001176306	SCV001340223	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-04-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002532809	SCV003292594	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2025-01-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533281	SCV004121129	uncertain significance	FBN1-related disorder	2023-01-26	criteria provided, single submitter	clinical testing	The FBN1 c.2600A>G variant is predicted to result in the amino acid substitution p.Asn867Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-48787397-T-C). 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.
All of Us Research Program, National Institutes of Health	RCV004002732	SCV004814890	uncertain significance	Marfan syndrome	2023-11-30	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 867 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 20/282852 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV004808802	SCV005436332	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	FBN1: PP2, BS2