Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019813 | SCV001181218 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-23 | criteria provided, single submitter | clinical testing | The p.L1101V variant (also known as c.3301C>G), located in coding exon 23 of the SMARCA4 gene, results from a C to G substitution at nucleotide position 3301. The leucine at codon 1101 is replaced by valine, an amino acid with highly similar properties. 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 |
RCV002550849 | SCV003285067 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2024-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1101 of the SMARCA4 protein (p.Leu1101Val). 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: 823512). 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) has been performed 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. |