ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.790G>A (p.Gly264Arg)

dbSNP: rs746036083
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000694019 SCV000822444 uncertain significance Rhabdoid tumor predisposition syndrome 2 2022-09-03 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 264 of the SMARCA4 protein (p.Gly264Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 572597). 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 disruptive.
Ambry Genetics RCV001026944 SCV001189422 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-31 criteria provided, single submitter clinical testing The p.G264R variant (also known as c.790G>A), located in coding exon 4 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 790. The glycine at codon 264 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001809757 SCV002056352 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing

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