Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV003152014 | SCV003840362 | uncertain significance | not provided | 2022-09-09 | 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; This variant is associated with the following publications: (PMID: 19245665) |
| Ambry Genetics | RCV004673861 | SCV005171212 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-08 | criteria provided, single submitter | clinical testing | The p.P15T variant (also known as c.43C>A), located in coding exon 2 of the SMARCE1 gene, results from a C to A substitution at nucleotide position 43. The proline at codon 15 is replaced by threonine, 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 tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV005099431 | SCV005808089 | uncertain significance | Familial meningioma | 2024-06-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 15 of the SMARCE1 protein (p.Pro15Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2443407). 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 not expected to disrupt SMARCE1 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. |