Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000807901 | SCV000947981 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1326 of the SMARCA4 protein (p.Glu1326Lys). 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: 652363). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMARCA4 protein function. 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 | RCV001021568 | SCV001183198 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | The p.E1326K variant (also known as c.3976G>A), located in coding exon 28 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 3976. The glutamic acid at codon 1326 is replaced by lysine, an amino acid with 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. |
| Genome- |
RCV001809822 | SCV002056892 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing |