Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000440158 | SCV000511636 | uncertain significance | not provided | 2016-09-08 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
Counsyl | RCV000672446 | SCV000797552 | uncertain significance | Peroxisome biogenesis disorder type 3B; Peroxisome biogenesis disorder 3A (Zellweger) | 2018-01-31 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000989843 | SCV001140434 | likely pathogenic | Peroxisome biogenesis disorder type 3B | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000440158 | SCV002009276 | pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001861489 | SCV002152700 | uncertain significance | Peroxisome biogenesis disorder 3A (Zellweger) | 2022-10-30 | criteria provided, single submitter | clinical testing | This variant, c.368_370del, results in the deletion of 1 amino acid(s) of the PEX12 protein (p.Leu123del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751058068, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PEX12-related conditions. ClinVar contains an entry for this variant (Variation ID: 377276). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282136 | SCV002572317 | uncertain significance | not specified | 2022-08-25 | criteria provided, single submitter | clinical testing | Variant summary: PEX12 c.368_370delTTC (p.Leu123del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 2e-05 in 251230 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, described as p.Leu123del, has been reported in the literature in the heterozygous state (i.e. without an identified second variant) in at-least one individual, who was affected with mild clinical phenotype of the Zellweger Syndrome spectrum (Soliman_2018). Authors of this study also performed functional studies with patient derived fibroblasts and demonstrated both peroxisomal- and Zellweger-like cytoplasmic catalase localization, decreased cellular peroxisome number, and additional cellular alterations (Soliman_2018). This report does not provide unequivocal conclusions about association of the variant with Zellweger Syndrome. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=3), likely pathogenic (n=1) and pathogenic (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |