Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000613201 | SCV000722073 | likely benign | not specified | 2017-08-15 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000613201 | SCV002051130 | uncertain significance | not specified | 2023-03-07 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.5918-12T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 250738 control chromosomes, predominantly at a frequency of 0.00012 within the Latino subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5918-12T>G in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV003767574 | SCV004571773 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-07-19 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004002533 | SCV004832236 | uncertain significance | Marfan syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | This variant causes a T to G nucleotide substitution at the -12 position of intron 48 of the FBN1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 4/250738 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. |