ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6888G>T (p.Gln2296His)

dbSNP: rs363830
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769624 SCV000901021 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-09-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769624 SCV001347011 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 2296 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 1/251298 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.
Fulgent Genetics, Fulgent Genetics RCV002487569 SCV002781005 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 2021-09-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002533951 SCV002981786 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-11-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004535896 SCV004118617 uncertain significance FBN1-related disorder 2023-08-01 criteria provided, single submitter clinical testing The FBN1 c.6888G>T variant is predicted to result in the amino acid substitution p.Gln2296His. A study evaluating the correlation between common single nucleotide polymorphisms (SNPs) and non-syndromic aortic dissection (AD), found that the minor allele frequency of this variant was significantly higher in affected individuals with the Stanford A AD subtype compared to healthy controls, but not in the Stanford B AD subtype (reported using rs363830 SNP ID in Pan et al. 2022. PubMed ID: 35154271). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-48720652-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV003999928 SCV004822419 uncertain significance Marfan syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 2296 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 1/251298 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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