Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001733358 | SCV001983406 | uncertain significance | not specified | 2021-09-23 | criteria provided, single submitter | clinical testing | Variant summary: FBN1 c.7840G>A (p.Ala2614Thr) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251062 control chromosomes (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.7840G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have 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. |
| Invitae | RCV002032727 | SCV002280571 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-11-19 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002477908 | SCV002791381 | 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 | 2021-10-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003163815 | SCV003863086 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-12-15 | criteria provided, single submitter | clinical testing | The p.A2614T variant (also known as c.7840G>A), located in coding exon 63 of the FBN1 gene, results from a G to A substitution at nucleotide position 7840. The alanine at codon 2614 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV004008976 | SCV004822281 | uncertain significance | Marfan syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 2614 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 2/251062 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. |