Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001179385 | SCV000319333 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2014-11-19 | criteria provided, single submitter | clinical testing | The c.4337-3A>C intronic variant results from an A to C substitution 3 nucleotides upstream from coding exon 35 in the FBN1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,494 samples (12,988 alleles) with coverage at this position. This nucleotide position is well conserved in available vertebrate species, though the C allele is present in wallaby and platypus. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Color Diagnostics, |
RCV001179385 | SCV001344039 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2019-01-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001859451 | SCV002221444 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-11-26 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 263868). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is present in population databases (rs770551687, gnomAD 0.01%). This sequence change falls in intron 35 of the FBN1 gene. It does not directly change the encoded amino acid sequence of the FBN1 protein. It affects a nucleotide within the consensus splice site. |
All of Us Research Program, |
RCV003995692 | SCV004830891 | likely benign | Marfan syndrome | 2023-06-26 | criteria provided, single submitter | clinical testing |