Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000801204 | SCV000940970 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2022-06-20 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 646837). This missense change has been observed in individual(s) with clinical features of PIGO-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 231 of the PIGO protein (p.Phe231Leu). |
Gene |
RCV001592988 | SCV001814769 | uncertain significance | not provided | 2020-08-18 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003413601 | SCV004113385 | uncertain significance | PIGO-related disorder | 2023-08-03 | criteria provided, single submitter | clinical testing | The PIGO c.693C>G variant is predicted to result in the amino acid substitution p.Phe231Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |