Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016411 | SCV001177366 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | The p.T910M variant (also known as c.2729C>T), located in coding exon 18 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 2729. The threonine at codon 910 is replaced by methionine, an amino acid with similar properties. One functional study showed compromised ATPase activity, which in turn affected the recruitment of the enzyme topoisomerase I to the chromatin (Husain A et al. Nat Commun 2016 Feb;7:10549). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003617820 | SCV004412177 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-02-20 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 910 of the SMARCA4 protein (p.Thr910Met). 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: 438790). 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) performed at Invitae indicates that this missense variant is expected to disrupt SMARCA4 protein function. Experimental studies have shown that this missense change affects SMARCA4 function (PMID: 23698369, 26842758). 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. |
| Donald Williams Parsons Laboratory, |
RCV000505663 | SCV000599957 | other | Medulloblastoma | 2016-05-01 | no assertion criteria provided | clinical testing |