Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481917 | SCV000570732 | uncertain significance | not provided | 2024-10-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Victorian Clinical Genetics Services, |
RCV002470871 | SCV002766970 | uncertain significance | Intellectual developmental disorder with autism and macrocephaly | 2020-05-26 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as a 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. NMD-predicted variants resulting in loss of protein function have previously been reported in this gene, however the mechanism for missese variants is currently unknown (ClinVar). (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from an alanine to a threonine (exon 14). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (1 heterozygote, 0 homozygote). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (Dead-like helicase N super family). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant is absent in the population and has previously been described as a variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Labcorp Genetics |
RCV000481917 | SCV004644722 | uncertain significance | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 421506). 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. 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 expected to disrupt CHD8 protein function. This variant has not been reported in the literature in individuals affected with CHD8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 922 of the CHD8 protein (p.Ala922Thr). |