ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.1435G>A (p.Gly479Arg) (rs147346327)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766966 SCV000250154 uncertain significance not provided 2018-06-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FBN2 gene. The G479R variant has not been published as pathogenic or been reported as benign to our knowledge. This variant has been identified in two other individuals referred for Marfan syndrome/TAAD testing at GeneDx, though both individuals harbored co-occurring variants and no segregation studies have been performed. The G479R 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In addition, this variant has been observed in 26/24036 (0.11%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016).
Ambry Genetics RCV000254070 SCV000320122 uncertain significance Cardiovascular phenotype 2019-03-22 criteria provided, single submitter clinical testing The p.G479R variant (also known as c.1435G>A), located in coding exon 10 of the FBN2 gene, results from a G to A substitution at nucleotide position 1435. The glycine at codon 479 is replaced by arginine, an amino acid with dissimilar properties, and is located in the EGF-like #4 domain. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV000286121 SCV000452638 likely benign Congenital contractural arachnodactyly 2018-01-12 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000199291 SCV000603698 uncertain significance not specified 2017-01-21 criteria provided, single submitter clinical testing
Invitae RCV000286121 SCV001004850 likely benign Congenital contractural arachnodactyly 2020-11-24 criteria provided, single submitter clinical testing

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