Submissions for variant NM_001999.4(FBN2):c.4249C>T (p.His1417Tyr)

dbSNP: rs863223572

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198694	SCV000250208	likely pathogenic	not provided	2014-03-24	criteria provided, single submitter	clinical testing	p.His1417Tyr (CAC>TAC): c.4249 C>T in exon 33 of the FBN2 gene (NM_001999.3) The H1417Y variant has not been published as a mutation or has it been reported as a benign polymorphism to our knowledge. The H1417Y variant was not observed 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 H1417Y 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Located in the EGF-like 23 calcium-binding domain, missense mutations in the same domain (D1408N, C1425R, C1425Y, 1425F) have been reported in association with congenital contractural arachnodactyly, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. This variant was found in TAAD
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277526	SCV002566578	uncertain significance	Connective tissue disorder	2022-07-19	criteria provided, single submitter	clinical testing