Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001191054 | SCV001358725 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-05-01 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 1397 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual suspected of having Marfan syndrome (PMID: 25652356). This variant has been identified in 3/251380 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293526 | SCV001482117 | uncertain significance | not specified | 2023-01-23 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.4190G>T (p.Gly1397Val) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251380 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4190G>T has been reported in the literature in a cohort of suspected or confirmed MFS patients, without strong evidence for causality (Baudhuin_2015). To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV001348656 | SCV001542965 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2024-01-29 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002497668 | SCV002791902 | uncertain significance | Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome | 2021-09-28 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004010479 | SCV004814752 | uncertain significance | Marfan syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with valine at codon 1397 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/251380 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. |