ClinVar Miner

Submissions for variant NM_001128849.2(SMARCA4):c.442G>A (p.Gly148Arg) (rs138689221)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204451 SCV000261340 likely benign Rhabdoid tumor predisposition syndrome 2 2020-12-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000267497 SCV000410454 benign Coffin-Siris syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics RCV000563484 SCV000663901 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-21 criteria provided, single submitter clinical testing The p.G148R variant (also known as c.442G>A), located in coding exon 3 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 442. The glycine at codon 148 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species.In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000204451 SCV000891051 likely benign Rhabdoid tumor predisposition syndrome 2 2021-01-06 criteria provided, single submitter clinical testing The SMARCA4 c.442G>A (p.Gly148Arg) missense change has a maximum subpopulation frequency of 0.077% in gnomAD v3.1 ( This population frequency is higher than expected for a pathogenic variant in SMARCA4 causing Rhabdoid Tumor Predisposition Syndrome (BS1). In silico tools predict a deleterious effect on the gene or protein function (PP3), however to our knowledge these predictions have not been confirmed by functional studies. This variant has been identified in one individual without a personal or family history of rhabdoid tumors or Coffin-Siris syndrome (internal data). It has also been observed in a case of atypical teratoid/rhabdoid tumor with an alternative molecular basis for disease (BP5; internal data). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS1, BP5, PP3.

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