Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001306575 | SCV001495953 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-08-18 | criteria provided, single submitter | clinical testing | 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: 1009133). 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 methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1319 of the SMARCA4 protein (p.Met1319Val). |
| Ambry Genetics | RCV002357112 | SCV002621943 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-11 | criteria provided, single submitter | clinical testing | The p.M1319V variant (also known as c.3955A>G), located in coding exon 28 of the SMARCA4 gene, results from an A to G substitution at nucleotide position 3955. The methionine at codon 1319 is replaced by valine, 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 variant remains unclear. |