Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567770 | SCV000675225 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-12 | criteria provided, single submitter | clinical testing | The p.Q323K variant (also known as c.967C>A), located in coding exon 7 of the SMARCB1 gene, results from a C to A substitution at nucleotide position 967. The glutamine at codon 323 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001859975 | SCV002221164 | uncertain significance | not provided | 2024-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 323 of the SMARCB1 protein (p.Gln323Lys). This variant is not present in population databases (gnomAD no frequency). 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: 486504). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SMARCB1 protein function with a negative predictive value of 80%. 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. |
| Baylor Genetics | RCV004568219 | SCV005052806 | uncertain significance | Rhabdoid tumor predisposition syndrome 1 | 2024-02-06 | criteria provided, single submitter | clinical testing |