Submissions for variant NM_000138.5(FBN1):c.2177A>G (p.Glu726Gly)

dbSNP: rs2505576546

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003783664	SCV004570935	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-02-20	criteria provided, single submitter	clinical testing	Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. This variant disrupts the p.Glu726 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 726 of the FBN1 protein (p.Glu726Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Marfan syndrome (PMID: 19293843). In at least one individual the variant was observed to be de novo.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004697312	SCV005196674	likely pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing