Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038836 | SCV000062514 | likely pathogenic | Primary dilated cardiomyopathy | 2010-10-28 | criteria provided, single submitter | clinical testing | The Asn220fs variant has not been reported in the literature nor been identified in any other family tested by our laboratory. This variant is predicted to caus e a frameshift, which alters the protein's amino acid sequence beginning at codo n 220 and leads to a premature stop codon 20 amino acids downstream. This altera tion is then predicted to lead to a truncated or absent protein. In addition, 3 out of 13 VCL variants previously identified in DCM patients are loss of functio n variants (LMM unpublished data). Therefore, the Asn220fs variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV001852813 | SCV002203852 | uncertain significance | Dilated cardiomyopathy 1W | 2024-12-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn220Lysfs*21) in the VCL gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in VCL cause disease. This variant is present in population databases (rs770713697, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of VCL-related conditions (PMID: 27532257, 30923642, 34495297). ClinVar contains an entry for this variant (Variation ID: 45618). 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. |
| Ambry Genetics | RCV004018879 | SCV005026015 | uncertain significance | Cardiovascular phenotype | 2023-11-21 | criteria provided, single submitter | clinical testing | The c.659dupA variant, located in coding exon 6 of the VCL gene, results from a duplication of A at nucleotide position 659, causing a translational frameshift with a predicted alternate stop codon (p.N220Kfs*21). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of VCL has not been established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |