Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519462 | SCV000616821 | likely pathogenic | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | 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: 27119594, 26633542, 34426522) |
Invitae | RCV000706539 | SCV000835596 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 893 of the PIGN protein (p.Ser893Arg). This variant is present in population databases (rs199573774, gnomAD 0.04%). This missense change has been observed in individual(s) with developmental and epileptic encephalopathy and/or PIGN-related disease (PMID: 35179230, 36322149; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 449082). 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 expected to disrupt PIGN protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV000706539 | SCV001440302 | likely pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2019-01-01 | criteria provided, single submitter | clinical testing | This variant was identified as compound heterozygous. |
Centogene AG - |
RCV000706539 | SCV002059820 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2019-04-23 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000519462 | SCV002771330 | uncertain significance | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |