ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7463A>G (p.Glu2488Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002863758 SCV003230841 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-13 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2488 of the FBN1 protein (p.Glu2488Gly). This missense change has been observed in individual(s) with Marfan syndrome (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu2488 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 2029363).

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