Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Revvity Omics, |
RCV003136539 | SCV003819259 | uncertain significance | not provided | 2023-07-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV005227895 | SCV005863240 | uncertain significance | Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 | 2024-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 611 of the SEC23B protein (p.Arg611Trp). This variant is present in population databases (rs771826357, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of congenital dyserythropoietic anemia type II (PMID: 29188620, 34365611). ClinVar contains an entry for this variant (Variation ID: 2435789). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SEC23B protein function. This variant disrupts the p.Arg611 amino acid residue in SEC23B. Other variant(s) that disrupt this residue have been observed in individuals with SEC23B-related conditions (PMID: 20941788, 29901818), which suggests that this may be a clinically significant amino acid residue. 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. |