Submissions for variant NM_001999.4(FBN2):c.672G>T (p.Met224Ile)

gnomAD frequency: 0.00002  dbSNP: rs371292311

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002313320	SCV000739010	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2017-04-03	criteria provided, single submitter	clinical testing	The p.M224I variant (also known as c.672G>T), located in coding exon 6 of the FBN2 gene, results from a G to T substitution at nucleotide position 672. The methionine at codon 224 is replaced by isoleucine, an amino acid with highly 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.
Invitae	RCV000797105	SCV000936646	likely benign	Congenital contractural arachnodactyly	2023-02-16	criteria provided, single submitter	clinical testing
GeneDx	RCV003226955	SCV003923602	uncertain significance	not provided	2022-11-07	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge