Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001065328 | SCV001230284 | uncertain significance | not provided | 2023-09-25 | 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 214 of the SMARCB1 protein (p.Thr214Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 859261). 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 SMARCB1 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 | RCV002365759 | SCV002658579 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-14 | criteria provided, single submitter | clinical testing | The p.T214M variant (also known as c.641C>T), located in coding exon 6 of the SMARCB1 gene, results from a C to T substitution at nucleotide position 641. The threonine at codon 214 is replaced by methionine, 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 deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153925 | SCV003843708 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing |