ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7210G>A (p.Asp2404Asn)

gnomAD frequency: 0.00004  dbSNP: rs530059069
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694961 SCV000823433 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-10-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000774499 SCV000908202 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-04-26 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 2404 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 performed for this variant. This variant has been reported in four individuals from the same family who were affected with Marfan syndrome (PMID: 25652356). This variant has also been identified in 20/282192 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, LabCorp RCV001293490 SCV001482070 uncertain significance not specified 2021-02-08 criteria provided, single submitter clinical testing Variant summary: FBN1 c.7210G>A (p.Asp2404Asn) results in a conservative amino acid change located in the EGF-like calcium-binding domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 250962 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in FBN1 causing Marfan Syndrome (6.4e-05 vs 0.00011), allowing no conclusion about variant significance. c.7210G>A has been reported in the literature in individuals affected with Marfan Syndrome (Baudhuin_2015). This report does not provide unequivocal conclusions about association of the variant with Marfan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002507209 SCV002816374 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 2021-09-30 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003999631 SCV004822394 uncertain significance Marfan syndrome 2023-06-28 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 2404 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 performed for this variant. This variant has been reported in four individuals from the same family who were affected with Marfan syndrome (PMID: 25652356). This variant has also been identified in 20/282192 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.

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