ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.161A>G (p.His54Arg)

dbSNP: rs1348866967
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 RCV000646886 SCV000768671 uncertain significance Rhabdoid tumor predisposition syndrome 2 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 54 of the SMARCA4 protein (p.His54Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. 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 missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SMARCA4-related disease. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV002397262 SCV002707355 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-01 criteria provided, single submitter clinical testing The p.H54R variant (also known as c.161A>G), located in coding exon 1 of the SMARCA4 gene, results from an A to G substitution at nucleotide position 161. The histidine at codon 54 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.