Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000602707 | SCV000731518 | likely pathogenic | Rare genetic deafness | 2017-08-10 | criteria provided, single submitter | clinical testing | The p.Arg206Gln variant in ACTG1 has now been identified by our laboratory to ha ve occurred de novo in 1 individual with congenital progressive sensorineural he aring loss and vestibular dysfunction. This variant has been identified in 1/111 396 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnom ad.broadinstitute.org). Please note that for diseases with clinical variability , reduced penetrance, or recessive inheritance, pathogenic variants may be prese nt at a low frequency in the general population. Computational prediction tools and conservation analysis suggest that the p.Arg206Gln variant may impact the pr otein, though this information is not predictive enough to determine pathogenici ty. Missense variants in the ACTG1 gene have been associated with two condition s: 1) Autosomal dominant progressive hearing loss and vestibular dysfunction (de Heer 2009); 2) Baraitser-Winter syndrome. In summary, though additional studies are required to fully establish its clinical significance, the p.Arg206Gln vari ant is likely pathogenic. |
| Invitae | RCV002295307 | SCV002595508 | likely pathogenic | Autosomal dominant nonsyndromic hearing loss 20; Baraitser-winter syndrome 2 | 2022-10-26 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt ACTG1 protein function. ClinVar contains an entry for this variant (Variation ID: 517300). This missense change has been observed in individual(s) with deafness (Invitae). In at least one individual the variant was observed to be de novo. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 206 of the ACTG1 protein (p.Arg206Gln). |
| Sangiuolo Lab - |
RCV002287431 | SCV002576544 | likely pathogenic | Baraitser-winter syndrome 2 | 2022-09-29 | no assertion criteria provided | clinical testing |