Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000624537 | SCV000742860 | likely pathogenic | Inborn genetic diseases | 2024-02-09 | criteria provided, single submitter | clinical testing | The c.589G>A (p.G197S) alteration is located in exon 4 (coding exon 3) of the ACTB gene. This alteration results from a G to A substitution at nucleotide position 589, causing the glycine (G) at amino acid position 197 to be replaced by a serine (S)._x000D_ _x000D_ for ACTB-related Baraitser-Winter syndrome; however, its clinical significance for ACTB-related pleiotropic malformation syndrome is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in an individual with features consistent with ACTB-related Baraitser-Winter syndrome (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. The p.G197S amino acid is located in the actin domain and is more disruptive than nearby known pathogenic variants (Han, 2015). Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
| Institute of Medical Genetics and Applied Genomics, |
RCV001268477 | SCV001447433 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001305813 | SCV001495161 | likely pathogenic | Baraitser-Winter syndrome 1 | 2023-05-08 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACTB protein function. ClinVar contains an entry for this variant (Variation ID: 522017). This missense change has been observed in individual(s) with clinical features of ACTB-related conditions and/or clinical features of Baraitser-Winter syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 197 of the ACTB protein (p.Gly197Ser). |
| Gene |
RCV001268477 | SCV001800943 | pathogenic | not provided | 2022-12-22 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25979418) |
| Laboratory of Medical Genetics, |
RCV001305813 | SCV002760063 | pathogenic | Baraitser-Winter syndrome 1 | 2022-11-29 | criteria provided, single submitter | research |