Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001876349 | SCV002118092 | pathogenic | not provided | 2021-06-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the CNGB3 protein. Other variant(s) that result in a similarly extended protein product (p.Glu729Metfs*99) have been determined to be pathogenic (Invitae). This suggests that these extensions are likely to be causative of disease. This variant has not been reported in the literature in individuals with CNGB3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the CNGB3 gene (p.Lys702Argfs*127). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the CNGB3 protein and extend the protein by 18 additional amino acid residues. |
| Victorian Clinical Genetics Services, |
RCV004594599 | SCV005086161 | pathogenic | Achromatopsia 3 | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with achromatopsia 3 (MIM#262300) (PMIDs: 16379026, 23805033). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0701 - Other downstream elongation variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Three elongation variant have been classified as pathogenic by a clinical laboratory in ClinVar, and another two elongation variants have been seen in families with achromatopsia in the literature (PMID: 28795510). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been classified as pathogenic by a clinical laboratory in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |