Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001060126 | SCV001224791 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2019-11-25 | 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. 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 C25"). This variant has not been reported in the literature in individuals with ALK-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 545 of the ALK protein (p.Ser545Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. |
Gene |
RCV001760020 | SCV001991455 | uncertain significance | not provided | 2019-07-25 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |