ClinVar Miner

Submissions for variant NM_003079.5(SMARCE1):c.1008G>C (p.Glu336Asp)

dbSNP: rs1323477202
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000809768 SCV000949943 uncertain significance Familial meningioma 2024-08-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 336 of the SMARCE1 protein (p.Glu336Asp). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 653913). 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 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.
Ambry Genetics RCV002424896 SCV002740879 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-03 criteria provided, single submitter clinical testing The p.E336D variant (also known as c.1008G>C), located in coding exon 9 of the SMARCE1 gene, results from a G to C substitution at nucleotide position 1008. The glutamic acid at codon 336 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not 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 meningiomas is unlikely.

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