Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001024338 | SCV001186336 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.M188V variant (also known as c.562A>G), located in coding exon 7 of the SMARCE1 gene, results from an A to G substitution at nucleotide position 562. The methionine at codon 188 is replaced by valine, 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. |
Labcorp Genetics |
RCV001245372 | SCV001418655 | uncertain significance | Familial meningioma | 2023-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 188 of the SMARCE1 protein (p.Met188Val). This variant is present in population databases (rs765003978, gnomAD 0.01%). 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: 825856). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Baylor Genetics | RCV001245372 | SCV004205057 | uncertain significance | Familial meningioma | 2023-05-05 | criteria provided, single submitter | clinical testing |