Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003339221 | SCV004057894 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2024-01-30 | criteria provided, single submitter | clinical testing | The p.L16P variant (also known as c.47T>C), located in coding exon 1 of the FBN1 gene, results from a T to C substitution at nucleotide position 47. The leucine at codon 16 is replaced by proline, an amino acid with similar properties. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one individual with features of Marfan syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Laboratory Medicine and Genetics, |
RCV005051289 | SCV005684867 | likely pathogenic | Marfan syndrome | 2025-01-02 | no assertion criteria provided | clinical testing | The NM_000138.5:c.47T>C is considered to be rare in the general population database (gnomAD v2.1.1). This variant was found in a patient with Marfan syndrome meeting revised Ghent criteria (aortic root dilatation and ectopia lentis) and his affected family members (Samsung Medical Center internal data). According to the ClinGen guidance for PP1/BS4 and PP4 criteria (PMID: 38103548), PP4 with weighted strength was applied. In summary, this variant was classified as a likely pathogenic variant for Marfan syndrome (PP2, PP4 with weighted strength, PM2_P). |