Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000645323 | SCV000364922 | 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 |
RCV000645323 | SCV000767066 | uncertain significance | Dilated cardiomyopathy 1W | 2021-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 429 of the VCL protein (p.Asp429Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs139371702, ExAC 0.004%). 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: 300787). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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 |
RCV002253381 | SCV002525364 | uncertain significance | not provided | 2022-05-25 | criteria provided, single submitter | clinical testing | Identified in a patient with dilated cardiomyopathy (Verdonschot et al., 2020); however, specific clinical information was not provided; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32880476) |
| Ambry Genetics | RCV002379170 | SCV002690831 | uncertain significance | Cardiovascular phenotype | 2024-04-27 | criteria provided, single submitter | clinical testing | The p.D429E variant (also known as c.1287T>A), located in coding exon 10 of the VCL gene, results from a T to A substitution at nucleotide position 1287. The aspartic acid at codon 429 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamic acid is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002502194 | SCV002816770 | uncertain significance | Dilated cardiomyopathy 1W; Hypertrophic cardiomyopathy 15 | 2021-09-10 | criteria provided, single submitter | clinical testing |