ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.3278G>A (p.Arg1093Gln)

dbSNP: rs1568498301
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001019599 SCV001180980 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-15 criteria provided, single submitter clinical testing The p.R1093Q variant (also known as c.3278G>A), located in coding exon 23 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 3278. The arginine at codon 1093 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001043136 SCV001206853 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-09-06 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMARCA4 protein function. ClinVar contains an entry for this variant (Variation ID: 823390). 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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1093 of the SMARCA4 protein (p.Arg1093Gln).
Genome-Nilou Lab RCV001809925 SCV002056862 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001019599 SCV002532886 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-09 criteria provided, single submitter curation
Baylor Genetics RCV001043136 SCV004204917 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-09-05 criteria provided, single submitter clinical testing

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