ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.8363C>T (p.Thr2788Met) (rs143007898)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617159 SCV000319265 likely benign Cardiovascular phenotype 2014-04-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification
Center for Medical Genetics Ghent,University of Ghent RCV000279195 SCV000787410 likely benign Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing
Color RCV000248624 SCV000913678 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-10-19 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the last exon of the FBN1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant 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 26/277156 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Illumina Clinical Services Laboratory,Illumina RCV000248624 SCV000392036 likely benign Thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000333030 SCV000392037 likely benign MASS syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000373725 SCV000392038 likely benign Stiff skin syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000279195 SCV000392039 likely benign Marfan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000338888 SCV000392040 likely benign Acromicric dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000399054 SCV000392041 likely benign Ectopia lentis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000284981 SCV000392042 likely benign Weill-Marchesani syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000339896 SCV000392043 likely benign Geleophysic dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589560 SCV000695622 benign not provided 2017-06-06 criteria provided, single submitter clinical testing Variant summary: The FBN1 c.8363C>T (p.Thr2788Met) variant alters a conserved nucleotide. The variant is located outside of any known functional domain or repeat, although 3/4 in silico tools (SNPs&GO not captured here due to low reliability) predict a damaging outcome for this variant. The variant of interest has been identified in a large, broad control datasets of ExAC and gnomAD at a similar frequencies of 0.0001071 (13/121406 chrs and 26/277156 chrs tested, respectively). In both datasets, the variant was identified exclusively in individuals of African ancestry (0.001249; 13/10406 chrs tested and 0.0009987; 24/24032). The observed frequencies exceed the estimated maximal expected allele frequency of a pathogenic FBN1 variant (0.0001), suggesting that the variant represents a rare ethnic-specific functional polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, but is sited as Likely Benign by clinical diagnostic laboratories/reputable databases. Taken together, this variant is classified as a Benign.

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