Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002265515 | SCV002547253 | uncertain significance | not provided | 2021-12-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29992558, 24658002) |
Ambry Genetics | RCV002427741 | SCV002743563 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing | The p.R906H variant (also known as c.2717G>A), located in coding exon 18 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 2717. The arginine at codon 906 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003774835 | SCV004616052 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-04-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMARCA4 protein function. ClinVar contains an entry for this variant (Variation ID: 1695880). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 906 of the SMARCA4 protein (p.Arg906His). |