Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000508231 | SCV000603626 | pathogenic | not provided | 2017-06-01 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000825613 | SCV000966965 | pathogenic | Marfan syndrome | 2018-03-23 | criteria provided, single submitter | clinical testing | The p.Cys2552X variant in FBN1 has been reported in 1 individual with clinical f eatures of Marfan syndrome (Regalado 2016) and was absent from large population studies. This variant has been reported in ClinVar by other clinical laboratorie s (Variation ID: 439701). This nonsense variant leads to a premature termination codon at position 2552, which is predicted to lead to a truncated or absent pro tein. Heterozygous loss of function of the FBN1 gene is an established disease m echanism in individuals with Marfan syndrome. In summary, this variant meets cri teria to be classified as pathogenic for Marfan syndrome in an autosomal dominan t manner based upon the predicted impact to the protein, presence in an affected individual, and absence from controls. ACMG/AMP Criteria applied (Richards 2015 ): PVS1; PM2; PS4_Supporting. |
| Ambry Genetics | RCV002395225 | SCV002671796 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2018-01-15 | criteria provided, single submitter | clinical testing | The p.C2552* pathogenic mutation (also known as c.7656C>A), located in coding exon 61 of the FBN1 gene, results from a C to A substitution at nucleotide position 7656. This changes the amino acid from a cysteine to a stop codon within coding exon 61. This alteration was detected in a proband reported to have type A aortic dissection, and family history of aortic dissection (Regalado ES et al. Clin. Genet., 2016 Jun;89:719-23). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| All of Us Research Program, |
RCV000825613 | SCV004828595 | pathogenic | Marfan syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 62 of the FBN1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with familial thoracic aortic aneurysm and dissection (PMID: 26621581) and in another individual affected with Marfan syndrome (PMID: 35943490). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of FBN1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| University of Washington Center for Mendelian Genomics, |
RCV000755192 | SCV000883021 | likely pathogenic | Congenital aneurysm of ascending aorta; Acute aortic dissection | 2016-01-20 | no assertion criteria provided | research |