ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2877C>A (p.Phe959Leu)

gnomAD frequency: 0.00001  dbSNP: rs1411365281
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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 RCV000535578 SCV000627873 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2017-06-19 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 959 of the FBN1 protein (p.Phe959Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a FBN1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on FBN1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV004802128 SCV005424856 uncertain significance Marfan syndrome 2024-03-05 criteria provided, single submitter clinical testing

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