Submissions for variant NM_000138.5(FBN1):c.1715-2A>G

dbSNP: rs2043733370

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001035658	SCV001198992	pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2022-09-01	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change affects an acceptor splice site in intron 14 of the FBN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of Marfan syndrome (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 834883). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Mayo Clinic Laboratories, Mayo Clinic	RCV001508389	SCV001714513	pathogenic	not provided	2019-06-09	criteria provided, single submitter	clinical testing	PVS1, PM2, PP3, PP4