ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6403G>A (p.Asp2135Asn) (rs746167150)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000617759 SCV000738806 uncertain significance Cardiovascular phenotype 2016-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000181564 SCV000233867 likely pathogenic not provided 2013-12-27 criteria provided, single submitter clinical testing p.Asp2135Asn (GAT>AAT): c.6403 G>A in exon 53 of the FBN1 gene (NM_000138.4) The D2135N variant in the FBN1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. D2135N was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. D2135N is a semi-conservative amino acid substitution as these residues share similar properties, but differ in size, charge, or other properties which may impact secondary structure. The D2135N residue is well conserved across species. In silico algorithms are not consistent in their predictions but at least two concur that D2135N is probably damaging to protein structure/function. Mutations in nearby residues (E2130K, V3136D, G2140E, G2140R) have been reported in association with Marfan syndrome, further supporting the functional importance of this region of the protein.In summary, while D2135N is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in TAAD panel(s).

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