Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001229101 | SCV001401537 | uncertain significance | Holoprosencephaly sequence | 2023-08-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FOXH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 956321). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FOXH1 protein function. 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. This variant is present in population databases (rs752459708, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 158 of the FOXH1 protein (p.Ser158Thr). |