Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001347322 | SCV001541577 | uncertain significance | Methylcobalamin deficiency type cblE | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 379 of the MTRR protein (p.Ile379Val). This variant is present in population databases (rs746404785, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MTRR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043242). 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Natera, |
RCV001347322 | SCV002077207 | uncertain significance | Methylcobalamin deficiency type cblE | 2020-04-17 | no assertion criteria provided | clinical testing |