Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000810532 | SCV000950742 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-09-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193505 | SCV001362390 | uncertain significance | not specified | 2019-08-26 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.1175C>G (p.Pro392Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 250242 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1175C>G has been reported in the literature in an individual who died of sudden cardiac death, with no-conclusive cause (Campuzano_2014). This report does not provide an unequivocal conclusion about association of the variant with Marfan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| All of Us Research Program, |
RCV004001725 | SCV004823073 | uncertain significance | Marfan syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 392 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with unexplained sudden cardiac death (PMID: 25447171). This variant has been identified in 8/250242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |