ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.3272A>G (p.Lys1091Arg)

dbSNP: rs1555781772
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
Ambry Genetics RCV000565212 SCV000672257 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-05 criteria provided, single submitter clinical testing The p.K1091R variant (also known as c.3272A>G), located in coding exon 23 of the SMARCA4 gene, results from an A to G substitution at nucleotide position 3272. The lysine at codon 1091 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001058254 SCV001222811 uncertain significance Rhabdoid tumor predisposition syndrome 2 2019-01-10 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 484947). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 1091 of the SMARCA4 protein (p.Lys1091Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine.
Genome-Nilou Lab RCV001809651 SCV002056859 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 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.