Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000468336 | SCV000549944 | uncertain significance | Holoprosencephaly sequence | 2016-11-17 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs769660425, ExAC 0.02%) but has not been reported in the literature in individuals with a FOXH1-related disease. This sequence change replaces serine with tyrosine at codon 265 of the FOXH1 protein (p.Ser265Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |