Submissions for variant NM_001999.4(FBN2):c.5495G>A (p.Arg1832His)

gnomAD frequency: 0.00007  dbSNP: rs140276399

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000559761	SCV000630238	benign	Congenital contractural arachnodactyly	2024-01-09	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659626	SCV000781466	uncertain significance	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000998428	SCV001154503	uncertain significance	not provided	2019-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000559761	SCV001316241	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000998428	SCV001777306	uncertain significance	not provided	2023-02-21	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (Callewaert et al., 2009; Frederic et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19006240, 18767143)
Ambry Genetics	RCV002350201	SCV002651010	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-12-02	criteria provided, single submitter	clinical testing	The p.R1832H variant (also known as c.5495G>A), located in coding exon 43 of the FBN2 gene, results from a G to A substitution at nucleotide position 5495. The arginine at codon 1832 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.