ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.4589T>A (p.Met1530Lys)

dbSNP: rs1600635680
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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 RCV001022892 SCV001184680 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-23 criteria provided, single submitter clinical testing The p.M1562K variant (also known as c.4685T>A), located in coding exon 32 of the SMARCA4 gene, results from a T to A substitution at nucleotide position 4685. The methionine at codon 1562 is replaced by lysine, an amino acid with similar 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). 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.
GeneDx RCV002222657 SCV002499893 uncertain significance not provided 2022-04-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as c.4589T>A, p.(M1530K); This variant is associated with the following publications: (PMID: 24658002)
Labcorp Genetics (formerly Invitae), Labcorp RCV002550005 SCV003215292 uncertain significance Rhabdoid tumor predisposition syndrome 2 2022-06-22 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1562 of the SMARCA4 protein (p.Met1562Lys). 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. 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 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: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 825095).

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