Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001007979 | SCV001167711 | pathogenic | not provided | 2020-09-02 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 73 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23561846, 24784135, 22305531, 32562213, 28441409, 24706016, 26545172, 31704190, 32256299) |
Invitae | RCV000022881 | SCV001217804 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2023-01-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects PIGA function (PMID: 22305531, 28441409). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 29988). This premature translational stop signal has been observed in individuals with PIGA-related multiple congenital anomalies-hypotonia-seizures syndrome (PMID: 22305531, 24706016, 26545172). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg412*) in the PIGA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acid(s) of the PIGA protein. |
Ce |
RCV001007979 | SCV001250207 | pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000022881 | SCV000044172 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2014-05-06 | no assertion criteria provided | literature only | |
Biochemical Molecular Genetic Laboratory, |
RCV000022881 | SCV001190768 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2020-02-05 | no assertion criteria provided | clinical testing |