ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3442A>G (p.Ser1148Gly)

gnomAD frequency: 0.00002  dbSNP: rs764809572
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198329 SCV000250191 uncertain significance not provided 2016-10-03 criteria provided, single submitter clinical testing The S1148G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant 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. The S1148G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position where only amino acids with similar properties to Serine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, while the S1148G variant is located within a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue within this domain. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with CCA (Collod-Beroud et al., 2003; Frédéric et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Ambry Genetics RCV001265725 SCV001443894 uncertain significance Inborn genetic diseases 2017-12-11 criteria provided, single submitter clinical testing
Invitae RCV001318629 SCV001509341 benign Congenital contractural arachnodactyly 2023-08-08 criteria provided, single submitter clinical testing

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