Submissions for variant NM_000138.5(FBN1):c.2884T>C (p.Tyr962His)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV003528051	SCV004357423	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-03-31	criteria provided, single submitter	clinical testing	This missense variant replaces tyrosine with histidine at codon 962 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 1/31360 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003779306	SCV004568744	benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-03-29	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004011455	SCV004814863	uncertain significance	Marfan syndrome	2024-06-09	criteria provided, single submitter	clinical testing	This missense variant replaces tyrosine with histidine at codon 962 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/31360 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV003528051	SCV005113156	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-05-08	criteria provided, single submitter	clinical testing	The p.Y962H variant (also known as c.2884T>C), located in coding exon 24 of the FBN1 gene, results from a T to C substitution at nucleotide position 2884. The tyrosine at codon 962 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.