ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.644G>A (p.Arg215Gln)

gnomAD frequency: 0.00001  dbSNP: rs753703844
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000658712 SCV000780498 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000773638 SCV000907332 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-10-18 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 215 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 1/251394 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001855381 SCV002109937 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-07-19 criteria provided, single submitter clinical testing This variant is present in population databases (rs753703844, gnomAD 0.003%). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 546752). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 215 of the FBN1 protein (p.Arg215Gln). 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 RCV004004193 SCV004823116 uncertain significance Marfan syndrome 2023-05-31 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the TGFbeta-like motif 1 of the FBN1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/246170 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.

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