ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.4562del (p.Pro1521fs) (rs886039035)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000242532 SCV000319739 pathogenic Cardiovascular phenotype 2015-06-01 criteria provided, single submitter clinical testing The c.4562delC pathogenic mutation, located in coding exon 36 of the FBN1 gene, results from a deletion of one nucleotide at nucleotide position 4562, causing a translational frameshift with a predicted alternate stop codon(p.P1521Qfs*60). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589783 SCV000695545 likely pathogenic Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections 2017-06-22 criteria provided, single submitter clinical testing Variant summary: The FBN1 c.4562delC (p.Pro1521Glnfs) variant results in a premature termination codon, predicted to cause a truncated or absent FBN1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.4621C>T [p.Arg1541X], c.4786C>T [p.Arg1596X], and c.4930C>T [p.Arg1644X]). One in silico tool predicts a damaging outcome for this variant. This variant is absent from the large control database ExAC (0/121160 control chromosomes). One clinical diagnostic laboratory has classified this variant as pathogenic. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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