ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.3844A>G (p.Asn1282Asp)

dbSNP: rs2075092306
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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 RCV001046059 SCV001209944 uncertain significance Rhabdoid tumor predisposition syndrome 2 2022-11-15 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 843434). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1282 of the SMARCA4 protein (p.Asn1282Asp). 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 RCV003339441 SCV004059227 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-29 criteria provided, single submitter clinical testing The p.N1282D variant (also known as c.3844A>G), located in coding exon 26 of the SMARCA4 gene, results from an A to G substitution at nucleotide position 3844. The asparagine at codon 1282 is replaced by aspartic acid, 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 SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). Based on the supporting evidence, the association of this alteration with Coffin-Siris syndrome is unknown; however, the association of this alteration with rhabdoid tumor predisposition syndrome is unlikely.

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