Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000153515 | SCV000203039 | other | not provided | 2017-01-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000153515 | SCV000519507 | benign | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | E429A, commonly reported as c.1298A>C, is a benign variant. It results in reduced MTHFR activity but it is not associated with increased plasma folate concentration in the heterozygous or homozygous state. This variant is present in 31% of alleles in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9545395, 18842806, 21241403, 22882325, 18836720, 21577095, 20135343, 23652803, 18992148, 23162020, 23771968, 19936946, 19837268, 20031554, 19232336, 19356065, 11875032, 22102315, 21897766, 21334398, 21845428, 20935396, 20532637, 21080081, 18583979, 21613384, 19854238, 21107737, 11395038, 9719624, 26238013, 27068821, 27330833, 23659764, 24109560, 23685927, 11274424, 29600437, 24440586, 22051736, 29395581, 20078877, 24175756, 24488901, 24301776, 22576927, 25573130, 29974397, 26135458, 23523621, 16489479) |
ARUP Laboratories, |
RCV000153515 | SCV000604289 | benign | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000350590 | SCV001135170 | benign | Neural tube defects, folate-sensitive | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000153515 | SCV001147148 | benign | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | MTHFR: BP4, BS1, BS2 |
Labcorp Genetics |
RCV001197542 | SCV001733272 | benign | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2025-02-03 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001197542 | SCV001748535 | benign | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2021-07-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001197542 | SCV002506414 | benign | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2023-12-06 | criteria provided, single submitter | clinical testing | ACMG categories: BA1, BP4 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000430863 | SCV004099611 | likely benign | not specified | 2023-09-07 | criteria provided, single submitter | clinical testing | Variant summary: MTHFR c.1286A>C (p.Glu429Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.29 in 251462 control chromosomes in the gnomAD database, including 11567 homozygotes strongly suggesting that the variant is benign. This variant, c.1286A>C is also known as 1298A>C. One publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity and homocysteine levels for heterozygotes and homozygotes were not different from those with the wild type genotype, supporting the idea that this polymorphism alone might not significantly affect homocysteine metabolism (example: Weisberg_2001). The following publication has been ascertained in the context of this evaluation (PMID: 11395038). Ten submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as Benign/likely benign (n=7), uncertain significance (n=1), risk factor (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Genomic Medicine Center of Excellence, |
RCV001197542 | SCV004805343 | benign | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2024-03-25 | criteria provided, single submitter | research | |
OMIM | RCV000003698 | SCV000023861 | benign | MTHFR THERMOLABILE POLYMORPHISM | 2008-07-01 | no assertion criteria provided | literature only | |
OMIM | RCV000003699 | SCV000023862 | risk factor | Schizophrenia, susceptibility to | 2008-07-01 | no assertion criteria provided | literature only | |
Department of Pharmacy and Biotechnology, |
RCV000144922 | SCV000187679 | uncertain significance | Gastrointestinal stromal tumor | flagged submission | case-control | ||
Centre for Mendelian Genomics, |
RCV001197542 | SCV001368321 | likely pathogenic | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2019-01-28 | flagged submission | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: No criteria apply. This variant was detected in homozygous state. |
Natera, |
RCV001197542 | SCV001455754 | benign | Homocystinuria due to methylene tetrahydrofolate reductase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000430863 | SCV001741945 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000430863 | SCV001919429 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000430863 | SCV001928366 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000430863 | SCV001956936 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000430863 | SCV002037998 | benign | not specified | no assertion criteria provided | clinical testing | ||
Prevention |
RCV003974792 | SCV004794374 | benign | MTHFR-related disorder | 2023-12-01 | no assertion criteria provided | clinical testing | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |