ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.869T>C (p.Ile290Thr)

gnomAD frequency: 0.00096  dbSNP: rs144899305
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000304993 SCV000458438 uncertain significance Disorders of Intracellular Cobalamin Metabolism 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000642243 SCV000763902 likely benign Methylcobalamin deficiency type cblE 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV001591019 SCV001824422 uncertain significance not provided 2021-06-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge, in association with a MTRR-related disorder; This variant is associated with the following publications: (PMID: 31063268, 27535533)
Ambry Genetics RCV002520386 SCV003743132 likely benign Inborn genetic diseases 2024-02-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001591019 SCV003800185 uncertain significance not provided 2022-05-05 criteria provided, single submitter clinical testing The MTRR c.869T>C; p.Ile290Thr variant (rs144899305), to our knowledge, is not reported in an individual with homocystinuria-megaloblastic anemia, but is reported in the literature in an individual with cleft lip (Marini 2019). This variant is reported in ClinVar (Variation ID: 354357) and is found in the non-Finnish European population with an allele frequency of 0.18% (233/129,162 alleles) in the Genome Aggregation Database. The isoleucine at codon 290 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.148). Due to limited information, the clinical significance of the p.Ile290Thr variant is uncertain at this time. References: Marini NJ et al. Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate. Am J Med Genet A. 2019 Jul;179(7):1260-1269. PMID: 31063268.
Baylor Genetics RCV000642243 SCV003836328 uncertain significance Methylcobalamin deficiency type cblE 2022-03-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV000642243 SCV001459125 likely benign Methylcobalamin deficiency type cblE 2020-05-01 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.