ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1733T>G (p.Ile578Arg)

dbSNP: rs886831673
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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 RCV002632693 SCV003505001 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-06-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 578 of the FBN1 protein (p.Ile578Arg). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
All of Us Research Program, National Institutes of Health RCV004009471 SCV004829080 uncertain significance Marfan syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with arginine at codon 578 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 not been identified 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.
Color Diagnostics, LLC DBA Color Health RCV005403290 SCV006064343 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-02-12 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with arginine at codon 578 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 not been identified 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV005405968 SCV006070371 uncertain significance Cardiovascular phenotype 2025-04-09 criteria provided, single submitter clinical testing PM1, PM2, PP2

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