ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.4207G>A (p.Glu1403Lys)

dbSNP: rs878854223
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000233431 SCV000286082 uncertain significance Rhabdoid tumor predisposition syndrome 2 2015-12-07 criteria provided, single submitter clinical testing In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMARCA4-related disease. This sequence change replaces glutamic acid with lysine at codon 1435 of the SMARCA4 protein (p.Glu1435Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine.
Ambry Genetics RCV002327119 SCV002630896 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-22 criteria provided, single submitter clinical testing The p.E1435K variant (also known as c.4303G>A), located in coding exon 30 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 4303. The glutamic acid at codon 1435 is replaced by lysine, an amino acid with similar properties. 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). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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.

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.