Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001856916 | SCV002213551 | pathogenic | not provided | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu498Cysfs*11) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 28795510). This variant is present in population databases (rs773381712, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with achromatopsia (PMID: 28795510). ClinVar contains an entry for this variant (Variation ID: 427662). For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV000497969 | SCV002768223 | pathogenic | Achromatopsia 3 | 2022-02-02 | 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. However, rare cases of monoallelic disease have been reported, which appear to cause a less severe phenotype (PMID: 16379026). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (2 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in two unrelated individuals. This variant has been observed in a compound heterozygous state in three affected members of one family with achromatopsia, and in one affected member of another family where it was also observed as compound heterozygous with the p.(Thr383Ilefs*13) variant (PMID: 28795510). (SP) 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 |
| Molecular Genetics Laboratory, |
RCV000497969 | SCV000575796 | pathogenic | Achromatopsia 3 | 2017-03-27 | no assertion criteria provided | research |