ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2902A>T (p.Thr968Ser)

gnomAD frequency: 0.00001  dbSNP: rs752117227
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000818664 SCV000959289 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-09-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 968 of the FBN1 protein (p.Thr968Ser). This variant is present in population databases (rs752117227, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 661278). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FBN1 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV001526021 SCV001736282 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-11-02 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 968 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 3/251440 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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