Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001867374 | SCV002133330 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2021-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 676 of the SMARCA4 protein (p.Ala676Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. 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. 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 C0"). 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 | RCV004946791 | SCV005506426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-07 | criteria provided, single submitter | clinical testing | The p.A676T variant (also known as c.2026G>A), located in coding exon 13 of the SMARCA4 gene, results from a G to A substitution at nucleotide position 2026. The alanine at codon 676 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |