ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4294G>A (p.Asp1432Asn)

gnomAD frequency: 0.00001  dbSNP: rs778145681
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001182174 SCV001347530 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-12-06 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the calcium-binding EGF-like motif 24 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 1/246160 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Fulgent Genetics, Fulgent Genetics RCV002505771 SCV002812890 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 2021-09-17 criteria provided, single submitter clinical testing
Invitae RCV003769998 SCV004571761 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-01-28 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 922236). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is present in population databases (rs778145681, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1432 of the FBN1 protein (p.Asp1432Asn).

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