Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000705766 | SCV000834780 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-09-29 | 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 1597 of the SMARCA4 protein (p.Glu1597Lys). 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. 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. ClinVar contains an entry for this variant (Variation ID: 581828). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). |
Ambry Genetics | RCV002334387 | SCV002639511 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-31 | criteria provided, single submitter | clinical testing | The p.E1597K variant (also known as c.4789G>A), located in coding exon 33 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 4789. The glutamic acid at codon 1597 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |