Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000226181 | SCV000286017 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2024-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 78 of the SMARCA4 protein (p.Ser78Pro). 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: 238401). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SMARCA4 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002444889 | SCV002732953 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-01 | criteria provided, single submitter | clinical testing | The p.S78P variant (also known as c.232T>C), located in coding exon 2 of the SMARCA4 gene, results from a T to C substitution at nucleotide position 232. The serine at codon 78 is replaced by proline, an amino acid with similar properties. This amino acid position is not well 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998518 | SCV005622998 | uncertain significance | not provided | 2024-12-02 | criteria provided, single submitter | clinical testing | The SMARCA4 c.232T>C (p.Ser78Pro) variant has been reported in the published literature in an individual with unspecified skin cancer (PMID: 33144586 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Fulgent Genetics, |
RCV005025383 | SCV005654271 | uncertain significance | Rhabdoid tumor predisposition syndrome 2; Intellectual disability, autosomal dominant 16; Otosclerosis 12 | 2024-04-16 | criteria provided, single submitter | clinical testing |