Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000443275 | SCV000516543 | pathogenic | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); 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: 24706016, 26923721, 32452540, 31175295, 29502866, 29656098) |
| Institute of Human Genetics Munich, |
RCV000119283 | SCV001150205 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2018-10-12 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000119283 | SCV001451531 | likely pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2019-01-16 | criteria provided, single submitter | clinical testing | The PIGA c.355C>T (p.Arg119Trp) variant is a missense variant that has been reported in a hemizygous state in one male who presented with facial dysmorphisms, thin corpus callosum, delayed myelination, early onset epilepsy, hypotonia and profound intellectual disability and in a heterozygous state in the individual's unaffected mother (Kato et al. 2014). Another affected male individual was found to be hemizygous for a different variant at the same amino acid residue, c.356G>A (p.Arg119Gln), and presented with similar features (Lin et al. 2018). The p.Arg119Trp variant is absent from the Genome Aggregation Database in a region of good sequence coverage so the variant is presumed to be rare. Functional impact of the variant was assessed by examining the surface expression of three different GPI-anchored proteins, FLAER, CD24 and CD16, in patient granulocytes by flow cytometry. The authors found decreased expression of at least two proteins, CD24 and CD16, as compared to normal controls (Kato et al. 2014). In addition, several in-silico tools predict the Arg119Trp change to be deleterious. Based on the collective evidence and application of the ACMG criteria, the p.Arg119Trp variant is classified as likely pathogenic for multiple congenital anomalies-hypotonia-seizures syndrome 2. |
| Genomic Medicine Center of Excellence, |
RCV004820831 | SCV005442096 | pathogenic | Paroxysmal nocturnal hemoglobinuria 1 | 2024-12-19 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000119283 | SCV000154718 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2014-05-06 | no assertion criteria provided | literature only |