ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.1035A>G (p.Ile345Met)

gnomAD frequency: 0.00001  dbSNP: rs140944718
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000816511 SCV000957024 uncertain significance Methylcobalamin deficiency type cblE 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 345 of the MTRR protein (p.Ile345Met). This variant is present in population databases (rs140944718, gnomAD 0.06%). 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: 659491). 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 not expected to disrupt MTRR 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 RCV003243331 SCV003938351 uncertain significance Inborn genetic diseases 2023-05-05 criteria provided, single submitter clinical testing The c.1035A>G (p.I345M) alteration is located in exon 7 (coding exon 6) of the MTRR gene. This alteration results from a A to G substitution at nucleotide position 1035, causing the isoleucine (I) at amino acid position 345 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003432776 SCV004153915 likely benign not provided 2023-09-01 criteria provided, single submitter clinical testing MTRR: BP4
Natera, Inc. RCV000816511 SCV001459129 uncertain significance Methylcobalamin deficiency type cblE 2020-03-11 no assertion criteria provided clinical testing

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.