ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.20C>G (p.Pro7Arg)

dbSNP: rs1568416569
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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 RCV001365427 SCV001561699 uncertain significance Rhabdoid tumor predisposition syndrome 2 2020-09-08 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 7 of the SMARCA4 protein (p.Pro7Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant has not been reported in the literature in individuals with SMARCA4-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C35"). 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 RCV002420804 SCV002724533 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.P7R variant (also known as c.20C>G), located in coding exon 1 of the SMARCA4 gene, results from a C to G substitution at nucleotide position 20. The proline at codon 7 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well 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.

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