Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000731506 | SCV000859335 | uncertain significance | not provided | 2018-01-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002535212 | SCV003444620 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2022-09-02 | 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. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of PIGA-congenital disorder of glycosylation (PMID: 28133863). ClinVar contains an entry for this variant (Variation ID: 595845). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 142 of the PIGA protein (p.Ala142Thr). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987687 | SCV004803461 | uncertain significance | not specified | 2024-01-16 | criteria provided, single submitter | clinical testing | Variant summary: PIGA c.424G>A (p.Ala142Thr) results in a non-conservative amino acid change located in the PIGA, GPI anchor biosynthesis domain (IPR013234) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183063 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.424G>A has been reported in the literature in at-least one individual affected with early onset epileptic encephalopathy with burst suppression (example: Olson_2017, and Rochtus_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28133863, 31957018). ClinVar contains an entry for this variant (Variation ID: 595845). Based on the evidence outlined above, the variant was classified as uncertain significance. |