Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000809958 | SCV000950144 | uncertain significance | Familial meningioma | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 405 of the SMARCE1 protein (p.Pro405Ala). This variant is present in population databases (rs767835921, gnomAD 0.002%). 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: 654067). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002352399 | SCV002657141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-24 | criteria provided, single submitter | clinical testing | The p.P405A variant (also known as c.1213C>G), located in coding exon 10 of the SMARCE1 gene, results from a C to G substitution at nucleotide position 1213. The proline at codon 405 is replaced by alanine, 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. 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 Coffin-Siris syndrome is unknown; however, the association of this alteration with an increased risk of meningiomas is unlikely. |
Baylor Genetics | RCV000809958 | SCV005052819 | uncertain significance | Familial meningioma | 2024-03-22 | criteria provided, single submitter | clinical testing |