Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000539175 | SCV000657553 | uncertain significance | TWIST1-related craniosynostosis; Saethre-Chotzen syndrome | 2017-04-16 | criteria provided, single submitter | clinical testing | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TWIST1-related disease. This sequence change replaces alanine with glutamic acid at codon 152 of the TWIST1 protein (p.Ala152Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. |
Gene |
RCV001770483 | SCV002001901 | uncertain significance | not provided | 2020-01-30 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |