ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.6833C>T (p.Thr2278Met) (rs2307109)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210681 SCV000263016 uncertain significance Inborn genetic diseases 2014-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
GeneDx RCV000489643 SCV000576524 uncertain significance not provided 2017-04-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FBN2 gene. The T2278M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 10/8644 (0.1%) alleles from individuals of East Asian ancestry in the Exome Aggregation Consortium (ExAC) datset (Lek et al., 2016; Exome Variant Server). This substitution occurs at a position that is conserved in mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, while the T2278M variant is located within a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a Cysteine residue in this domain. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with congenital arachnodactyly (Collod-Beroud et al., 2003; Frédéric et al., 2009). Nevertheless, the T2278M 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.
Invitae RCV000489643 SCV001005592 likely benign not provided 2018-06-01 criteria provided, single submitter clinical testing
Invitae RCV001439397 SCV001642282 likely benign Congenital contractural arachnodactyly 2020-10-15 criteria provided, single submitter clinical testing

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