Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001304753 | SCV001494047 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1207 of the SMARCA4 protein (p.Val1207Ile). This variant is present in population databases (rs201974258, gnomAD 0.007%). 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: 1007557). 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 | RCV002451686 | SCV002617489 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-30 | criteria provided, single submitter | clinical testing | The p.V1207I variant (also known as c.3619G>A), located in coding exon 25 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 3619. The valine at codon 1207 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |