Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003618357 | SCV004405020 | uncertain significance | Holoprosencephaly 5 | 2022-10-31 | 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. 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 ZIC2 protein function. This variant has not been reported in the literature in individuals affected with ZIC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 437 of the ZIC2 protein (p.Pro437Leu). |
| Ambry Genetics | RCV004371649 | SCV004983957 | uncertain significance | Inborn genetic diseases | 2023-09-20 | criteria provided, single submitter | clinical testing | The c.1310C>T (p.P437L) alteration is located in exon 3 (coding exon 3) of the ZIC2 gene. This alteration results from a C to T substitution at nucleotide position 1310, causing the proline (P) at amino acid position 437 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |