Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000704837 | SCV000364935 | uncertain significance | Dilated cardiomyopathy 1W | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000704837 | SCV000833807 | uncertain significance | Dilated cardiomyopathy 1W | 2025-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 669 of the VCL protein (p.Arg669Gln). This variant is present in population databases (rs759771302, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with VCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 300793). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Gene |
RCV001548587 | SCV001768525 | uncertain significance | not provided | 2021-04-26 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 300793; Landrum et al., 2016) |
| New York Genome Center | RCV002467726 | SCV002764480 | uncertain significance | Dilated cardiomyopathy 1W; Hypertrophic cardiomyopathy 15 | 2021-12-20 | criteria provided, single submitter | clinical testing | The heterozygous c.2006G>A (p.Arg669Gln) missense variant identified in the VCL gene has not been reported in affected individuals in the literature. The variant has 0.00001315 allele frequency in the gnomAD(v3) database (2 out of 152046 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. This variant has been reported in the ClinVar database as a variant of uncertain significance [Variation ID: 300793]. The variant affects a conserved residue and multiple in silico prediction tools provide conflicting predictions about potential pathogenicity ofthis variant (CADD score = 29.8, REVEL score = 0.179). Based on the available evidence, the heterozygous c.2006G>A (p.Arg669Gln) missense variant identified inthe VCL gene is reported as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV003165817 | SCV003871840 | uncertain significance | Cardiovascular phenotype | 2024-12-31 | criteria provided, single submitter | clinical testing | The c.2006G>A (p.R669Q) alteration is located in exon 14 (coding exon 14) of the VCL gene. This alteration results from a G to A substitution at nucleotide position 2006, causing the arginine (R) at amino acid position 669 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Dept of Medical Biology, |
RCV003318374 | SCV004022088 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PM2 |