ClinVar Miner

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

dbSNP: rs1342399494
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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
Labcorp Genetics (formerly Invitae), Labcorp 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 (https://gnomad.broadinstitute.org). In summary, this variant meets criteria to be classified as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.