Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001867799 | SCV002136348 | uncertain significance | not provided | 2024-06-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 277 of the PPP3CA protein (p.Ile277Val). This variant is present in population databases (rs540250871, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PPP3CA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1369039). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PPP3CA protein function with a negative predictive value of 80%. 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. |
| Fulgent Genetics, |
RCV002490045 | SCV002782551 | uncertain significance | Developmental and epileptic encephalopathy 91; Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development | 2021-08-30 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005409056 | SCV006071723 | uncertain significance | not specified | 2025-03-12 | criteria provided, single submitter | clinical testing | Variant summary: PPP3CA c.829A>G (p.Ile277Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-06 in 238924 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.829A>G in individuals affected with Epileptic Encephalopathy, Infantile Or Early Childhood, 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1369039). Based on the evidence outlined above, the variant was classified as uncertain significance. |