Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019918 | SCV001181333 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-31 | criteria provided, single submitter | clinical testing | The p.Q331H variant (also known as c.993G>T), located in coding exon 5 of the SMARCA4 gene, results from a G to T substitution at nucleotide position 993. The glutamine at codon 331 is replaced by histidine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001860963 | SCV002293491 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2021-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with histidine at codon 331 of the SMARCA4 protein (p.Gln331His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 823564). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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. |