ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6052G>A (p.Val2018Ile) (rs363802)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756138 SCV000883859 uncertain significance not provided 2018-04-12 criteria provided, single submitter clinical testing The FBN1 c.6052G>A, p.Val2018Ile variant (rs363802) has not been reported in the medical literature, but is listed in ClinVar (Variation ID: 200073). It is observed in the Genome Aggregation Database general population database at a frequency of 0.14 percent in the Latino population (48/34352 alleles). The valine at residue 2018 is highly conserved, but computational algorithms (Align GVGD, PolyPhen-2, SIFT) predict that the variant has minimal impact on the protein. Due to the limited information regarding this variant, its clinical significance could not be determined with certainty.
GeneDx RCV000756138 SCV000233859 uncertain significance not provided 2016-10-20 criteria provided, single submitter clinical testing p.Val2018Ile (GTC>ATC): c.6052 G>A in exon 50 of the FBN1 gene (NM_000138.4)A variant of unknown significance has been identified in the FBN1 gene. The V2018I variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The V2018I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Missense pathogenic variants in nearby residues (D2013Y, E2016K, C2017R, E2019K, I2023T) have been reported in association with Marfan syndrome, supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, the V2018I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and occurs at a position that is conserved in mammals.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.The variant is found in TAAD panel(s).
Invitae RCV000546191 SCV000627950 likely benign Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2017-12-19 criteria provided, single submitter clinical testing

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