ClinVar Miner

Submissions for variant NM_003079.5(SMARCE1):c.995A>C (p.Lys332Thr)

dbSNP: rs766656583
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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 RCV001954635 SCV002195985 uncertain significance Familial meningioma 2021-06-03 criteria provided, single submitter clinical testing This variant is present in population databases (rs766656583, ExAC 0.01%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMARCE1-related conditions. This sequence change replaces lysine with threonine at codon 332 of the SMARCE1 protein (p.Lys332Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine.
Ambry Genetics RCV002386736 SCV002688868 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-21 criteria provided, single submitter clinical testing The p.K332T variant (also known as c.995A>C), located in coding exon 9 of the SMARCE1 gene, results from an A to C substitution at nucleotide position 995. The lysine at codon 332 is replaced by threonine, an amino acid with 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 an increased risk of Coffin-Siris syndrome is unknown; however, the association of this alteration with meningiomas is unlikely.

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