Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000701708 | SCV000830520 | uncertain significance | Infantile spasms | 2024-03-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 726 of the PIK3AP1 protein (p.Thr726Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 578637). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| New York Genome Center | RCV001839020 | SCV002099392 | uncertain significance | not provided | 2021-03-05 | criteria provided, single submitter | clinical testing | The inherited c.2177C>G (p.Thr726Arg) variant in exon 15 of 17 of PIK3AP1 has not been reported in affected individuals in the available literature. This variant is present in gnomAD at a low frequency (4/152062 heterozygotes, allele frequency =0.0000263, no homozygotes), suggesting it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Benign (REVEL; score: 0.024) and Tolerated (SIFT; score: 0.234). This variant was reported once in ClinVar database as a variant of uncertain significance (VarID:578637). Given the current evidence regarding its pathogenicity, the inherited c.2177C>G (p.Thr726Arg) variant identified in the PIK3AP1 gene is classified as a Variant of Uncertain Significance. |