ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.3480dup (p.Leu1161fs)

dbSNP: rs797045982
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194222 SCV000248964 pathogenic Rhabdoid tumor predisposition syndrome 2 2014-10-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV003338458 SCV004059295 pathogenic Hereditary cancer-predisposing syndrome 2023-08-24 criteria provided, single submitter clinical testing The c.3480dupG pathogenic mutation, located in coding exon 24 of the SMARCA4 gene, results from a duplication of G at nucleotide position 3480, causing a translational frameshift with a predicted alternate stop codon (p.L1161Afs*15). In a cohort of patients with small cell carcinoma of the ovary-hypercalcemic type (SCCOHT), this variant was identified in one case with reportedly non-familial SCCOHT (Witkowski L et al. Nat Genet, 2014 May;46:438-43). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Loss-of-function variants in SMARCA4 are known to cause rhabdoid tumor predisposition syndrome including SCCOHT; however, such associations with neurodevelopmental disorders 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). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is pathogenic for rhabdoid tumor predisposition syndrome; however, the association of this alteration with Coffin-Siris syndrome is unlikely.
Baylor Genetics RCV000194222 SCV005052744 pathogenic Rhabdoid tumor predisposition syndrome 2 2024-02-16 criteria provided, single submitter clinical testing

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.