ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2531T>C (p.Ile844Thr)

gnomAD frequency: 0.00001  dbSNP: rs751564716
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183157 SCV001348814 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-07-20 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 844 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 5/282452 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 RCV001586028 SCV001810984 uncertain significance not provided 2019-11-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV003770018 SCV004568000 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-07-26 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008354 SCV004814896 uncertain significance Marfan syndrome 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 844 of the FBN1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). 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 5/282452 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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