ClinVar Miner

Submissions for variant NM_000254.3(MTR):c.1325C>A (p.Ala442Glu)

dbSNP: rs770004849
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001758731 SCV001996980 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002540417 SCV003031801 uncertain significance Methylcobalamin deficiency type cblG 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 442 of the MTR protein (p.Ala442Glu). This variant is present in population databases (rs770004849, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1311222). 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 MTR 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.
Ambry Genetics RCV004641689 SCV005146692 uncertain significance Inborn genetic diseases 2024-06-17 criteria provided, single submitter clinical testing The c.1325C>A (p.A442E) alteration is located in exon 14 (coding exon 14) of the MTR gene. This alteration results from a C to A substitution at nucleotide position 1325, causing the alanine (A) at amino acid position 442 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.