ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5305G>A (p.Glu1769Lys)

dbSNP: rs2141260472
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001916691 SCV002191674 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-02-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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 missense change has been observed in individual(s) with clinical features of Marfan syndrome (Invitae). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1769 of the FBN1 protein (p.Glu1769Lys).
Department of Laboratory Medicine and Genetics, Samsung Medical Center RCV005050463 SCV005684890 likely pathogenic Marfan syndrome 2025-01-02 no assertion criteria provided clinical testing The NM_000138.5:c.5305G>A is considered to be rare in the general population database (gnomAD v2.1.1). This variant is predicted to be deletrious by in-silico analysis (REVEL). This variant is located in functional domains. This variant was found in a patient with known Marfan syndrome (PMID: 11933199). In summary, this variant was classified as a likely pathogenic variant for Marfan syndrome (PM1, PP2, PP3, PS4_P, PM2_P).

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