ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.1909G>A (p.Gly637Arg)

gnomAD frequency: 0.00001  dbSNP: rs917552239
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001013652 SCV001174267 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-13 criteria provided, single submitter clinical testing The p.G637R variant (also known as c.1909G>A), located in coding exon 11 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 1909. The glycine at codon 637 is replaced by arginine, an amino acid with dissimilar 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.
Invitae RCV001070647 SCV001235911 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-08-14 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 820319). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 637 of the SMARCA4 protein (p.Gly637Arg). 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt SMARCA4 protein function. 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.
Genome-Nilou Lab RCV001809909 SCV002056470 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing

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