Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000465791 | SCV000548386 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2016-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with threonine at codon 1422 of the SMARCA4 protein (p.Lys1422Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMARCA4-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |