Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001189729 | SCV000738864 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-06-25 | criteria provided, single submitter | clinical testing | The p.A373T variant (also known as c.1117G>A), located in coding exon 9 of the FBN1 gene, results from a G to A substitution at nucleotide position 1117. The alanine at codon 373 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001189729 | SCV001357082 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-09 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 373 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 7/251242 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 |
RCV001347916 | SCV001542197 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004002723 | SCV004823081 | uncertain significance | Marfan syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 373 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 7/251242 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004525987 | SCV005039475 | uncertain significance | not specified | 2024-03-12 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.1117G>A (p.Ala373Thr) results in a non-conservative amino acid change located in the TB domain (IPR017878) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251242 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1117G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 519753). Based on the evidence outlined above, the variant was classified as uncertain significance. |