ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.6681A>G (p.Thr2227=) (rs145681607)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197133 SCV000250233 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing The c.6681 A>G variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The c.6681 A>G variant was not observed with any significant frequency 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. While c.6681 A>G results in a silent amino acid change (T2227T), it is predicted to create a cryptic splice donor site, which may lead to abnormal gene splicing. Splice site mutations have been reported in the FBN2 gene in association with congenital contractural arachnodactyly. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Therefore, without clinical information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD,FBN2
Ambry Genetics RCV000249531 SCV000319348 uncertain significance Cardiovascular phenotype 2019-07-19 criteria provided, single submitter clinical testing The c.6681A>G variant (also known as p.T2227T), located in coding exon 53, results from an A to G substitution at nucleotide position 6681 of the FBN2 gene. This nucleotide substitution does not change the amino acid at codon 2227. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to significantly strengthen an alternate splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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