ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5441A>G (p.Asn1814Ser)

gnomAD frequency: 0.00001  dbSNP: rs775463311
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000631993 SCV000753096 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-09-21 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001805765 SCV002052523 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-09-07 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1814 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 2/251208 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health RCV004003818 SCV004814659 uncertain significance Marfan syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1814 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251208 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004722994 SCV005331852 uncertain significance not provided 2023-11-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (PMID: 12938084); This variant is associated with the following publications: (PMID: 12938084)

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