Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003749736 | SCV004552776 | uncertain significance | 46,XY sex reversal 9 | 2024-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 488 of the ZFPM2 protein (p.Ile488Thr). This variant is present in population databases (rs775854541, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ZFPM2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV004374339 | SCV004983241 | uncertain significance | Inborn genetic diseases | 2024-02-17 | criteria provided, single submitter | clinical testing | The c.1463T>C (p.I488T) alteration is located in exon 8 (coding exon 8) of the ZFPM2 gene. This alteration results from a T to C substitution at nucleotide position 1463, causing the isoleucine (I) at amino acid position 488 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |