ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.737-25CT[2]

dbSNP: rs72041020
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000244015 SCV000302588 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV001722286 SCV000723810 benign not provided 2018-06-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000244015 SCV001361374 benign not specified 2019-09-16 criteria provided, single submitter clinical testing Variant summary: FBN1 c.737-21_737-20delCT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.03 in 222242 control chromosomes in the gnomAD database, including 47 homozygotes. The observed variant frequency is approximately 263- fold the estimated maximal allele frequency expected for a pathogenic variant in FBN1 causing Aortopathy phenotype (0.00011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.737-21_737-20delCT in individuals affected with Aortopathy and no experimental evidence demonstrating an impact on protein function have been reported. Two other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories cited the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001722286 SCV001477709 benign not provided 2023-11-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002057314 SCV002462189 benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-02-01 criteria provided, single submitter clinical testing

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