Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV000678420 | SCV005655154 | likely pathogenic | Autosomal recessive congenital ichthyosis 5 | 2024-05-18 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689851 | SCV005185693 | pathogenic | Lamellar ichthyosis | 2024-05-16 | criteria provided, single submitter | clinical testing | Variant summary: CYP4F22 c.177C>G (p.Phe59Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249736 control chromosomes. c.177C>G has been reported in the literature in the homozygous state in multiple individuals affected with Lamellar Ichthyosis (e.g. Lefevre_2006, Seidl-Philipp_2020, Mohamad_2021). These data indicate that the variant is very likely to be associated with disease. At least one functional study reports that the variant results in <20% activity compared to the wild-type protein (e.g. Ohno_2015). The following publications have been ascertained in the context of this evaluation (PMID: 16436457, 33786896, 26056268, 31642606). ClinVar contains an entry for this variant (Variation ID: 560326). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Genomic Medicine Center of Excellence, |
RCV000678420 | SCV004805131 | pathogenic | Autosomal recessive congenital ichthyosis 5 | 2024-03-17 | criteria provided, single submitter | research | |
| Gene |
RCV001731881 | SCV001981890 | pathogenic | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | Published functional studies of F59L demonstrate a significant decrease of enzyme activity (Ohno et al., 2015); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31168818, 16436457, 31130284, 33067036, 26056268) |
| Baylor Genetics | RCV000678420 | SCV001523987 | pathogenic | Autosomal recessive congenital ichthyosis 5 | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Hadassah Hebrew University Medical Center | RCV000678420 | SCV001430591 | likely pathogenic | Autosomal recessive congenital ichthyosis 5 | 2019-06-20 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004758722 | SCV005348349 | likely pathogenic | CYP4F22-related disorder | 2024-09-12 | no assertion criteria provided | clinical testing | The CYP4F22 c.177C>G variant is predicted to result in the amino acid substitution p.Phe59Leu. This variant has been reported in the homozygous state in individuals with autosomal recessive congenital ichthyosis (Lefevre et al. 2006. PubMed ID: 16436457; Table S1, Monies et al. 2019. PubMed ID: 31130284; Table S2a, Seidl-Philipp et al. 2019. PubMed ID: 31642606; Table S2, Simpson et al. 2019. PubMed ID: 31168818). In vitro functional studies demonstrated that expression of this variant resulted in a decrease of omega-hydroxylase activity to <20% of the wild-type protein (Ohno et al. 2015. PubMed ID: 26056268). This variant is reported in 0.00088% of alleles in individuals of European (non-Finnish) descent in gnomAD, and is interpreted as pathogenic/likely pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/560326/). This variant is interpreted as likely pathogenic. |
| Biochemical Molecular Genetic Laboratory, |
RCV000678420 | SCV001190815 | pathogenic | Autosomal recessive congenital ichthyosis 5 | 2020-02-05 | no assertion criteria provided | clinical testing | |
| Institute for Human Genetics, |
RCV000678420 | SCV000804491 | pathogenic | Autosomal recessive congenital ichthyosis 5 | 2018-04-23 | no assertion criteria provided | clinical testing |