Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017787 | SCV001178932 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-24 | criteria provided, single submitter | clinical testing | The p.V995I variant (also known as c.2983G>A), located in coding exon 20 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 2983. The valine at codon 995 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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. |
| Invitae | RCV001050078 | SCV001214166 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2022-03-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 822429). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 995 of the SMARCA4 protein (p.Val995Ile). |
| Genome- |
RCV001809915 | SCV002056850 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002282426 | SCV002571360 | uncertain significance | not provided | 2022-03-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; De novo variant with confirmed parentage; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; This variant is associated with the following publications: (PMID: 24658002) |