Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV004786827 | SCV005401457 | pathogenic | not provided | 2024-05-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; 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: 30733661, 38592426) |
| Labcorp Genetics |
RCV003085948 | SCV003472518 | likely pathogenic | Baraitser-Winter syndrome 1 | 2025-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 171 of the ACTB protein (p.Leu171Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Baraitser-Winter syndrome (PMID: 30733661). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 2159436). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ACTB protein function with a negative predictive value of 80%. 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. |
| OMIM | RCV003324586 | SCV004030173 | pathogenic | ACTB-associated syndromic thrombocytopenia | 2023-08-24 | no assertion criteria provided | literature only |