ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.5275A>C (p.Lys1759Gln) (rs201113098)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198829 SCV000250220 uncertain significance not provided 2018-12-04 criteria provided, single submitter clinical testing p.Lys1759Gln (K1759Q) (AAA>CAA): c.5275 A>C in exon 41 of the FBN2 gene (NM_001999.3) The K1759Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The K1759Q 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. The K1759Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, this substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In addition, missense mutations in nearby residues have not been reported in association with a FBN2-associated disorder, indicating that this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-PANCARD
Invitae RCV000463573 SCV000553171 likely benign Congenital contractural arachnodactyly 2020-10-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618549 SCV000738947 uncertain significance Cardiovascular phenotype 2020-03-16 criteria provided, single submitter clinical testing The p.K1759Q variant (also known as c.5275A>C), located in coding exon 41 of the FBN2 gene, results from an A to C substitution at nucleotide position 5275. The lysine at codon 1759 is replaced by glutamine, an amino acid with similar properties. 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 alteration remains unclear.

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