ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7876C>G (p.Leu2626Val)

dbSNP: rs2042898824
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176546 SCV001340565 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-06-14 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 2626 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 not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001233931 SCV001406549 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 2626 of the FBN1 protein (p.Leu2626Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001176546 SCV002676832 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-04-16 criteria provided, single submitter clinical testing The p.L2626V variant (also known as c.7876C>G), located in coding exon 63 of the FBN1 gene, results from a C to G substitution at nucleotide position 7876. The leucine at codon 2626 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
Fulgent Genetics, Fulgent Genetics RCV002491500 SCV002780571 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 2022-01-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004006306 SCV004844939 uncertain significance Marfan syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces leucine with valine at codon 2626 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 cardiovascular disorders in the literature. This variant has not been identified 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.

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