ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2683A>G (p.Ile895Val)

gnomAD frequency: 0.00001  dbSNP: rs772308703
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176116 SCV001339960 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-12 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 895 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 3/250962 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 RCV002221614 SCV002498947 uncertain significance not provided 2022-02-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN1 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003)
Fulgent Genetics, Fulgent Genetics RCV002483946 SCV002778290 uncertain significance Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2021-07-14 criteria provided, single submitter clinical testing
Invitae RCV003769872 SCV004604100 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-07-13 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000323 SCV004814883 uncertain significance Marfan syndrome 2023-10-02 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 895 of the FBN1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/250962 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.

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