Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001894570 | SCV002135158 | uncertain significance | Microphthalmia with brain and digit anomalies; Orofacial cleft 11 | 2021-08-07 | 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. 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. This variant has not been reported in the literature in individuals affected with BMP4-related conditions. This variant is present in population databases (rs774455359, ExAC 0.003%). This sequence change replaces arginine with tryptophan at codon 159 of the BMP4 protein (p.Arg159Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |