Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000627243 | SCV000748234 | likely pathogenic | not provided | 2018-02-08 | criteria provided, single submitter | clinical testing | The E2841X likely pathogenic variant in the FBN1 gene has been reported in a Japanese individual evaluated for suspected Marfan syndrome (Ogawa et al., 2011); however, no specific clinical details were provided. The E2841X variant is located in the last exon of the FBN1 gene and is predicted to result in an abnormal, truncated protein product. If the protein produced is stable, the expected result is loss of the last 31 amino acid residues. Other downstream nonsense and frameshift variants in the FBN1 gene have been reported in Human Gene Mutation Database in association with Marfan syndrome and TAAD (Stenson et al., 2014). Furthermore, the E2841X variant is not observed in large population cohorts (Lek et al., 2016). |
| Ce |
RCV000627243 | SCV001250255 | pathogenic | not provided | 2017-03-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002408641 | SCV002675459 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2023-01-05 | criteria provided, single submitter | clinical testing | The p.E2841* pathogenic mutation (also known as c.8521G>T), located in coding exon 65 of the FBN1 gene, results from a G to T substitution at nucleotide position 8521. This changes the amino acid from a glutamic acid to a stop codon within coding exon 65. This alteration occurs at the 3' terminus of theFBN1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 31 amino acids (1%) of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This mutation has been previously reported in a cohort of patients with suspected or confirmed Marfan syndrome (Ogawa N et al. Am. J. Cardiol. 2011;108:1801-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Blueprint Genetics | RCV000143895 | SCV000188764 | pathogenic | Marfan syndrome | 2014-01-29 | no assertion criteria provided | clinical testing |