ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.1757_1760del (p.Lys586fs)

dbSNP: rs1342399494
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657489 SCV000779224 pathogenic not provided 2023-05-26 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28873162, 24658001, 24658002, 31954538, 34308366)
Department of Pediatrics, Memorial Sloan Kettering Cancer Center RCV001523822 SCV001478184 likely pathogenic Rhabdoid tumor predisposition syndrome 2 2020-12-15 criteria provided, single submitter research
Invitae RCV001523822 SCV002232057 pathogenic Rhabdoid tumor predisposition syndrome 2 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys586Argfs*26) in the SMARCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 545889). For these reasons, this variant has been classified as Pathogenic.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001523822 SCV003928119 pathogenic Rhabdoid tumor predisposition syndrome 2 2023-04-20 criteria provided, single submitter clinical testing The SMARCA4 c.1757_1760del (p.Lys586ArgfsTer26) change deletes four nucleotides to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation or absence of protein due to nonsense-mediated decay. This variant has been reported in an individual with a rhabdoid tumor whose tumor harbored a second pathogenic variant in the SMARCA4 gene (internal data). This variant has a maximum subpopulation frequency of 0.0009% in gnomAD v2.1.1 ( In summary, this variant meets criteria to be classified as pathogenic.

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