Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029693 | SCV000052345 | likely pathogenic | Marfan syndrome | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
| Gene |
RCV000414055 | SCV000491619 | pathogenic | not provided | 2016-10-25 | criteria provided, single submitter | clinical testing | The c.1211delC pathogenic variant in the FBN1 gene has not been previously reported to our knowledge. However, this variant has been classified in ClinVar as a likely pathogenic variant by another clinical laboratory (ClinVar SCV000052345.1; Landrum et al., 2016). In addition, a different nucleotide change in the FBN1 gene that results in the same frameshift (c.1206delT, p.Pro404HisfsX44) has been reported in the literature in association with Marfan syndrome (Baumgartner et al., 2006; Magyar et al., 2009).The c.1211delC variant causes a shift in reading frame starting at codon Proline 404, changing it to a Histidine, and creating a premature stop codon at position 44 of the new reading frame, denoted p.Pro404HisfsX44. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Multiple other downstream frameshift variants in the FBN1 gene have been reported in HGMD in association with Marfan syndrome (Stenson et al., 2014). Furthermore, the c.1211delC variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.1211delC in the FBN1 gene is interpreted as a pathogenic variant. |