ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.8099C>T (p.Pro2700Leu)

dbSNP: rs886038782
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV005257996 SCV000317683 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2025-01-10 criteria provided, single submitter clinical testing The p.P2700L variant (also known as c.8099C>T), located in coding exon 64 of the FBN1 gene, results from a C to T substitution at nucleotide position 8099. The proline at codon 2700 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001218947 SCV001390857 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2700 of the FBN1 protein (p.Pro2700Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 263390). 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 not expected to disrupt FBN1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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