ClinVar Miner

Submissions for variant NM_001387283.1(SMARCA4):c.4266G>A (p.Lys1422=)

gnomAD frequency: 0.00001  dbSNP: rs896036433
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568399 SCV000675156 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-08 criteria provided, single submitter clinical testing The c.4266G>A variant (also known as p.K1422K), located in coding exon 29 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 4266. This nucleotide substitution does not change the at codon 1422. However, this change occurs in the last base pair of coding exon 29, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is conserved on limited sequence alignment. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003617840 SCV004522893 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-02-11 criteria provided, single submitter clinical testing This sequence change affects codon 1422 of the SMARCA4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SMARCA4 protein. This variant also falls at the last nucleotide of exon 30, which is part of the consensus splice site for this exon. 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. ClinVar contains an entry for this variant (Variation ID: 486458). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 30, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). 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.

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.