Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000558729 | SCV000637320 | uncertain significance | Familial meningioma | 2022-12-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 383 of the SMARCE1 protein (p.Ser383Asn). ClinVar contains an entry for this variant (Variation ID: 463420). 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 not expected to disrupt SMARCE1 protein function. |
Ambry Genetics | RCV003380609 | SCV004088630 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-26 | criteria provided, single submitter | clinical testing | The p.S383N variant (also known as c.1148G>A), located in coding exon 10 of the SMARCE1 gene, results from a G to A substitution at nucleotide position 1148. The serine at codon 383 is replaced by asparagine, 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. Missense and in-frame variants in SMARCE1 are known to cause neurodevelopmental disorders; however, such associations with increased risk of meningiomas are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Smith JM et al. Nat Genet. 2013 Mar;45(3):295-8). Based on the supporting evidence, the association of this alteration with an increased risk of Coffin-Siris syndrome is unknown; however, the association of this alteration with an increased risk of meningiomas is unlikely. |
Baylor Genetics | RCV000558729 | SCV005052829 | uncertain significance | Familial meningioma | 2023-11-29 | criteria provided, single submitter | clinical testing |