Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomics, |
RCV000768103 | SCV000899018 | uncertain significance | Transcobalamin II deficiency | 2021-03-30 | criteria provided, single submitter | clinical testing | TCN2 NM_000355.3 exon 8 p.Gly390Arg (c.1168G>A):This variant has not been reported in the literature but is present in 5/17248 East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs367605153). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Invitae | RCV000768103 | SCV002269530 | uncertain significance | Transcobalamin II deficiency | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 390 of the TCN2 protein (p.Gly390Arg). This variant is present in population databases (rs367605153, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 626028). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |