Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825546 | SCV000966863 | likely pathogenic | Congenital dyserythropoietic anemia | 2018-06-27 | criteria provided, single submitter | clinical testing | The p.Leu360TrpfsX3 variant in SEC23B has not been previously reported in indivi duals with congenital dyserythropoietic anemia and was absent from large populat ion studies. This variant is predicted to cause a frameshift, which alters the p rotein?s amino acid sequence beginning at position 360 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the SEC23 B gene is an established disease mechanism in congenital dyserythropoietic anemi a. In summary, this variant meets our criteria to be classified as likely pathog enic for congenital dyserythropoietic anemia in an autosomal recessive manner ba sed on the predicted impact on the protein and absence from controls. ACMG/AMP C riteria applied: PVS1, PM2. |
| Labcorp Genetics |
RCV003768553 | SCV004580859 | pathogenic | Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 | 2023-06-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu360Trpfs*3) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 666985). This variant has not been reported in the literature in individuals affected with SEC23B-related conditions. |