Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001313184 | SCV001503668 | uncertain significance | Joubert syndrome 15 | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 334 of the CEP41 protein (p.Gly334Arg). This variant is present in population databases (rs564625875, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CEP41-related conditions. ClinVar contains an entry for this variant (Variation ID: 1014451). 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 CEP41 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Gene |
RCV001773624 | SCV002002363 | uncertain significance | not provided | 2020-07-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Joe Di |
RCV001313184 | SCV001976523 | pathogenic | Joubert syndrome 15 | no assertion criteria provided | clinical testing | "CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium" (Lee et al. 2012). Lee et al. (2012) reported 8 patients from 3 consanguineous families with Joubert syndrome. All patients had hypotonia, ataxia, psychomotor delay with mental retardation, and the molar tooth sign on brain imaging. Additionally, "Joubert syndrome-15 is an autosomal recessive developmental disorder characterized by ataxia, hypotonia, delayed psychomotor development, and variable mental retardation. Other features, such as polydactyly, breathing abnormalities, and oculomotor apraxia, are variable" (summary by Lee et al., 2012). The c.1000G>A variant in CEP41 been observed in compound heterozygosity with c.1037A>G. As a compound heterozygote in an individual with abnormal brain MRI findings, this variant is classified as pathogenic based on functional studies. |