Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000210727 | SCV000262843 | pathogenic | Inborn genetic diseases | 2013-11-11 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003460433 | SCV004198757 | likely pathogenic | Neural tube defects, folate-sensitive | 2023-07-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000007446 | SCV004292804 | likely pathogenic | Methylcobalamin deficiency type cblE | 2023-08-28 | 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 487 of the MTRR protein (p.Gly487Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cobalamin E deficiency (PMID: 10484769, 12555939). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 7030). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MTRR protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000007446 | SCV000027646 | pathogenic | Methylcobalamin deficiency type cblE | 2002-10-01 | no assertion criteria provided | literature only |