ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.7181T>C (p.Ile2394Thr) (rs28763926)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194253 SCV000247368 likely benign not specified 2015-04-23 criteria provided, single submitter clinical testing
GeneDx RCV000194253 SCV000250129 uncertain significance not specified 2017-01-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FBN2 gene. The I2394T variant has not been published as pathogenic or been reported as benign to our knowledge. The I2394T variant is observed in 0.3-0.4% alleles from individuals of European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position where amino acids with similar properties to isoleucine are tolerated across species and in silico analysis suggests that this variant likely does not alter the protein structure/function. The I2394T variant does not affect a Cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene. 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 I2394T 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 RCV000228339 SCV000287277 likely benign Congenital contractural arachnodactyly 2020-12-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000194253 SCV000308645 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000241684 SCV000317904 likely benign Cardiovascular phenotype 2018-09-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000228339 SCV000452553 benign Congenital contractural arachnodactyly 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514088 SCV000609686 likely benign not provided 2017-03-06 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659630 SCV000781470 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283109 SCV001158784 benign none provided 2019-10-13 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000514088 SCV001798757 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000514088 SCV001808075 likely benign not provided no assertion criteria provided clinical testing

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