Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497601 | SCV000590436 | uncertain significance | not provided | 2017-06-15 | criteria provided, single submitter | clinical testing | The P105L variant in the CYP4F22 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P105L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P105L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P105L as a variant of uncertain significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731721 | SCV001983708 | uncertain significance | not specified | 2021-09-02 | criteria provided, single submitter | clinical testing | Variant summary: CYP4F22 c.314C>T (p.Pro105Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251494 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.314C>T has been reported in the literature in individuals affected with Lamellar Ichthyosis (Hotz_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Institute for Human Genetics, |
RCV000678407 | SCV000804478 | pathogenic | Autosomal recessive congenital ichthyosis 5 | 2018-04-23 | no assertion criteria provided | clinical testing |