Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000823057 | SCV000963896 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2025-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 311 of the SMARCA4 protein (p.Pro311Arg). This variant is present in population databases (rs759754994, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 664876). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SMARCA4 protein function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV001019175 | SCV001180500 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-05 | criteria provided, single submitter | clinical testing | The p.P311R variant (also known as c.932C>G), located in coding exon 5 of the SMARCA4 gene, results from a C to G substitution at nucleotide position 932. The proline at codon 311 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Genome- |
RCV001809845 | SCV002056381 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing |