Submissions for variant NM_170707.4(LMNA):c.937-7C>G (rs267607681)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color	RCV000772012	SCV000904968	uncertain significance	Cardiomyopathy	2018-04-13	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This variant occurs in the intron 5 splice acceptor region of the PCSK9 gene. Computational splicing tools suggest that this variant may have an impact on RNA splicing. An in vitro functional assay demonstrated the potential for this variant to impact splicing (PMID 28679633). However this variant has not been reported in individuals affected with cardiovascular disease in the literature. This variant has been identified in 11/273306 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057488	SCV000088602	not provided	not provided		no assertion provided	not provided
GeneDx	RCV000440584	SCV000513494	likely benign	not specified	2017-06-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000530832	SCV000657827	uncertain significance	Charcot-Marie-Tooth disease, type 2	2018-12-12	criteria provided, single submitter	clinical testing	This sequence change falls in intron 5 of the LMNA gene. It does not directly change the encoded amino acid sequence of the LMNA protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with cardiomyopathy (PMID: 28679633). ClinVar contains an entry for this variant (Variation ID: 66959). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.