Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000633319 | SCV000754540 | uncertain significance | Holoprosencephaly sequence | 2019-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 20 of the FOXH1 protein (p.Pro20Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FOXH1-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. |
| Ambry Genetics | RCV002533185 | SCV003737072 | uncertain significance | Inborn genetic diseases | 2022-03-16 | criteria provided, single submitter | clinical testing | The c.58C>T (p.P20S) alteration is located in exon 1 (coding exon 1) of the FOXH1 gene. This alteration results from a C to T substitution at nucleotide position 58, causing the proline (P) at amino acid position 20 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |