Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236256 | SCV001408972 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2019-11-12 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with SMARCA4-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 1570 of the SMARCA4 protein (p.Thr1570Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV002339650 | SCV002637625 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-14 | criteria provided, single submitter | clinical testing | The p.T1570I variant (also known as c.4709C>T), located in coding exon 32 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 4709. The threonine at codon 1570 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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. |