Submissions for variant NM_014000.2(VCL):c.1708C>T (p.Arg570Ter) (rs794729191)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184000	SCV000236494	uncertain significance	not provided	2018-11-20	criteria provided, single submitter	clinical testing	p.Arg570Stop (CGA>TGA): c.1708 C>T in exon 12 of the VCL gene (NM_014000.2).The R570X variant in the VCL gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. R570X was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R570X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. However, other nonsense mutations in the VCL gene have not been reported in association with cardiomyopathy.With the clinical and molecular information available at this time, we cannot definitively determine if R570X is a disease-causing mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s).
Invitae	RCV000530068	SCV000645847	uncertain significance	Dilated cardiomyopathy 1W	2017-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 570 (p.Arg570*) of the VCL gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a VCL-related disease. ClinVar contains an entry for this variant (Variation ID: 202161). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in VCL cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance.