Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SIB Swiss Institute of Bioinformatics | RCV000522028 | SCV000883157 | likely pathogenic | Glycosylphosphatidylinositol biosynthesis defect 15 | 2018-10-15 | criteria provided, single submitter | curation | This variant is interpreted as Likely Pathogenic, for Glycosylphosphatidylinositol biosynthesis defect 15, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/29100095). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM5 => Missense substitution changing Leu to Pro at a position adiacent to a residue where a likely pathogenic Leu to Pro change has been observed before. |
| Gene |
RCV001731749 | SCV001982100 | uncertain significance | not provided | 2021-09-27 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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: 32637629, 29100095) |
| Invitae | RCV001731749 | SCV003440913 | uncertain significance | not provided | 2022-07-26 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 453253). This missense change has been observed in individual(s) with clinical features of congenital disorders of glycosylation (PMID: 29100095, 32637629). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.005%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 290 of the GPAA1 protein (p.Leu290Pro). |
| OMIM | RCV000522028 | SCV000622107 | pathogenic | Glycosylphosphatidylinositol biosynthesis defect 15 | 2017-12-18 | no assertion criteria provided | literature only |