Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002890225 | SCV003243348 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 20; Baraitser-winter syndrome 2 | 2021-12-08 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ACTG1-related conditions. This variant is present in population databases (rs782069591, gnomAD 0.08%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 231 of the ACTG1 protein (p.Ala231Val). |
Laboratory of Prof. |
RCV004821328 | SCV005442606 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 20 | 2024-12-15 | criteria provided, single submitter | research | The ACTG1 c.692C>T:p.(Ala231Val) variant is predicted deleterious by most prediction tools and is very rare, with the highest prevalence among Ashkenazi Jews, suggesting a founder effect in this population. There are many known dominant missense pathogenic variants in the same region of the gene. The heterozygous variant was detected in an individual with sloping mild-to-severe hearing loss. |
Fulgent Genetics, |
RCV002890225 | SCV005652796 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 20; Baraitser-winter syndrome 2 | 2024-01-12 | criteria provided, single submitter | clinical testing |