ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.6805A>G (p.Met2269Val) (rs943225631)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497407 SCV000590201 uncertain significance not provided 2017-06-15 criteria provided, single submitter clinical testing The M2269V variant in the FBN2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M2269V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M2269V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret M2269V as a variant of uncertain significance.
Ambry Genetics RCV000622243 SCV000739032 uncertain significance Cardiovascular phenotype 2017-05-25 criteria provided, single submitter clinical testing The p.M2269V variant (also known as c.6805A>G), located in coding exon 54 of the FBN2 gene, results from an A to G substitution at nucleotide position 6805. The methionine at codon 2269 is replaced by valine, an amino acid with highly similar properties, and is located in a cbEGF-like domain. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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