Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001226339 | SCV001398651 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1462 of the SMARCA4 protein (p.Ser1462Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with features of Coffin-Siris syndrome (PMID: 32369273). ClinVar contains an entry for this variant (Variation ID: 953964). 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 | RCV002327536 | SCV002633030 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-12 | criteria provided, single submitter | clinical testing | The p.S1462N variant (also known as c.4385G>A), located in coding exon 30 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 4385. The serine at codon 1462 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |