ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4817-14T>G

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002957988 SCV003272674 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-03-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003331406 SCV004039136 likely benign not specified 2023-08-14 criteria provided, single submitter clinical testing Variant summary: FBN1 c.4817-14T>G alters a non-conserved nucleotide located at a position not widely known to affect splicing. Three our of four 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 4e-06 in 251274 control chromosomes. 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.4817-14T>G in individuals affected with FBN1-related condiitons and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
All of Us Research Program, National Institutes of Health RCV004007716 SCV004834796 uncertain significance Marfan syndrome 2023-10-06 criteria provided, single submitter clinical testing This variant causes a T to G nucleotide substitution at the -14 position of intron 39 of the FBN1 gene. 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 2/282670 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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