Submissions for variant NM_014000.3(VCL):c.622+4C>G

dbSNP: rs201020802

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000219947	SCV000272905	uncertain significance	not specified	2015-08-17	criteria provided, single submitter	clinical testing	The c.622+4C>G variant in VCL has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 5/66734 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs20 1020802). This variant is located in the 5' splice region. Computational tools d o not suggest an impact to splicing, though this information is not predictive e nough to rule out pathogenicity. In summary, the clinical significance of the c. 622+4C>G variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000545486	SCV000645871	uncertain significance	Dilated cardiomyopathy 1W	2023-08-23	criteria provided, single submitter	clinical testing	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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 229632). This variant has not been reported in the literature in individuals affected with VCL-related conditions. This variant is present in population databases (rs201020802, gnomAD 0.009%). This sequence change falls in intron 5 of the VCL gene. It does not directly change the encoded amino acid sequence of the VCL protein. It affects a nucleotide within the consensus splice site.
GeneDx	RCV001557305	SCV001779043	likely benign	not provided	2020-10-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365163	SCV002659413	uncertain significance	Cardiovascular phenotype	2023-01-04	criteria provided, single submitter	clinical testing	The c.622+4C>G intronic variant results from a C to G substitution 4 nucleotides after coding exon 5 in the VCL gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001557305	SCV001978546	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000219947	SCV001979246	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001557305	SCV001979716	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001557305	SCV001980400	likely benign	not provided		no assertion criteria provided	clinical testing