Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001218573 | SCV001390461 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1465 of the SMARCA4 protein (p.Lys1465Asn). 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: 947484). 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 C35"). |
| Ambry Genetics | RCV002327512 | SCV002628782 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-27 | criteria provided, single submitter | clinical testing | The p.K1465N variant (also known as c.4395G>T), located in coding exon 30 of the SMARCA4 gene, results from a G to T substitution at nucleotide position 4395. The lysine at codon 1465 is replaced by asparagine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |