Table 1.
Mutations reported in the MTHFR gene causing a severe 5-10-MTHFR deficiency.
| Disorder | Amino acid change | Nucleotide change | Mutation type | Exon/Intron | Domain | |
|---|---|---|---|---|---|---|
| 1 | MTHFR deficiency | Arg6* | c.16A>T | Non-sense | Exon 1 | Serine rich |
| 2 | MTHFR deficiency | Arg46Gln | c.137G>A | Missense | Exon 1 | Catalytic |
| 3 | MTHFR deficiency | Arg46Trp | c.136C>T | Missense | Exon 1 | Catalytic |
| 4 | MTHFR deficiency | Trp59Cys | c.177G>T | Missense | Exon 1 | Catalytic |
| 5 | MTHFR deficiency | Trp59Ser | c.176G>C | Missense | Exon 1 | Catalytic |
| 6 | MTHFR deficiency | Pro66Leu | c.197C>T | Missense | Exon 1 | Catalytic |
| 7 | MTHFR deficiency | Arg68Gly | c.202C>G | Missense | Exon 1 | Catalytic |
| 8 | MTHFR deficiency | Ser78* | c.233C>G | Non-sense | Exon 1 | Catalytic |
| 9 | MTHFR deficiency | Arg82Trp | c.244C>T | Missense | Exon 2 | Catalytic |
| 10 | MTHFR deficiency | Ala113Thr | c.337G>A | Missense | Exon 2 | Catalytic |
| 11 | MTHFR deficiency | Ala116Thr | c.346G>A | Missense | Exon 2 | Catalytic |
| 12 | MTHFR deficiency | His127Tyr | c.379C>T | Missense | Exon 2 | Catalytic |
| 13 | MTHFR deficiency | Thr129Asn | c.386C>A | Missense | Exon 2 | Catalytic |
| 14 | MTHFR deficiency | Thr139Met | c.416C>T | Missense | Exon 2 | Catalytic |
| 15 | MTHFR deficiency | Gln147Pro | c.440A>C | Missense | Exon 2 | Catalytic |
| 16 | MTHFR deficiency | Ala175Thr | c.523G>A | Missense | Exon 3 | Catalytic |
| 17 | MTHFR deficiency | His181Asp | c.541C>G | Missense | Exon3 | Catalytic |
| 18 | MTHFR deficiency | Arg183Gln | c.548G>A | Missense | Exon 3 | Catalytic |
| 19 | MTHFR deficiency | Cys193Tyr | c.578G>A | Missense | Exon 3 | Catalytic |
| 20 | MTHFR deficiency | Ala195Val | c.584C>T | Missense | Exon 3 | Catalytic |
| 21 | MTHFR deficiency | Gly196Asp | c.587G>A | Missense | Exon 3 | Catalytic |
| 22 | MTHFR deficiency | Pro202Thr | c.604C>A | Missense | Exon 4 | Catalytic |
| 23 | MTHFR deficiency | Ile225Leu | c.673A>C | Missense | Exon 4 | Catalytic |
| 24 | MTHFR deficiency | Ala233Gly | c.698C>G | Missense | Exon 4 | Catalytic |
| 25 | MTHFR deficiency | Val253Phe | c.757G>T | Missense | Exon 4 | Catalytic |
| 26 | MTHFR deficiency | Pro254Ser | c.760C>T | Missense | Exon 4 | Catalytic |
| 27 | MTHFR deficiency | Gly255Val | c.764G>T | Missense | Exon 4 | Catalytic |
| 28 | MTHFR deficiency | Ile256Asn | c.767T>A | Missense | Exon 4 | Catalytic |
| 29 | MTHFR deficiency | Phe257Val | c.769T>G | Missense | Exon 4 | Catalytic |
| 30 | MTHFR deficiency | Asn324Ser | c.971A>G | Missense | Exon 5 | Catalytic |
| 31 | MTHFR deficiency | Leu333Pro | c.998T>C | Missense | Exon 5 | Catalytic |
| 32 | MTHFR deficiency | Arg335His | c.1004G>A | Missense | Exon 5 | Catalytic |
| 33 | MTHFR deficiency | Trp339Gly | c.1015T>G | Missense | Exon 5 | Catalytic |
| 34 | MTHFR deficiency | Arg345Cys | c.1033C>T | Missense | Exon 5 | Catalytic |
| 35 | MTHFR deficiency | Pro348Ser | c.1042C>T | Missense | Exon 6 | Regulatory |
| 36 | MTHFR deficiency | His354Tyr | c.1060C>T | Missense | Exon 6 | Regulatory |
| 37 | MTHFR deficiency | Arg357His | c.1070G>A | Missense | Exon 6 | Regulatory |
| 38 | MTHFR deficiency | Arg358* | c.1072C>T | Non-sense | Exon 6 | Regulatory |
| 39 | MTHFR deficiency | Arg363His | c.1088G>A | Missense | Exon 6 | Regulatory |
| 40 | MTHFR deficiency | Lys372Glu | c.1114A>G | Missense | Exon 6 | Regulatory |
| 41 | MTHFR deficiency | Tyr374* | c.1122C>G | Non-sense | Exon 6 | Regulatory |
| 42 | MTHFR deficiency | Arg377His | c.1130G>A | Missense | Exon 6 | Regulatory |
| 43 | MTHFR deficiency | Trp381Arg | c.1141T>C | Missense | Exon 6 | Regulatory |
| 44 | MTHFR deficiency | Gly387Asp | c.1160G>A | Missense | Exon 6 | Regulatory |
| 45 | MTHFR deficiency | Trp421Ser | c.1262G>C | Missense | Exon 7 | Regulatory |
| 46 | MTHFR deficiency | Ser440Leu | c.1319C>T | Missense | Exon 7 | Regulatory |
| 47 | MTHFR deficiency | Glu470* | c.1408G>T | Non-sense | Exon 8 | Regulatory |
| 48 | MTHFR deficiency | Tyr506Asp | c.1516T>G | Missense | Exon 8 | Regulatory |
| 49 | MTHFR deficiency | Tyr512Cys | c.1535A>G | Missense | Exon 9 | Regulatory |
| 50 | MTHFR deficiency | Arg535Gln | c.1604G>A | Missense | Exon 9 | Regulatory |
| 51 | MTHFR deficiency | Arg535Trp | c.1603C>T | Missense | Exon 9 | Regulatory |
| 52 | MTHFR deficiency | Val536Phe | c.1606G>T | Missense | Exon 9 | Regulatory |
| 53 | MTHFR deficiency | Trp561* | c.1683G>A | Non-sense | Exon 10 | Regulatory |
| 54 | MTHFR deficiency | Arg567* | c.1699C>T | Non-sense | Exon 10 | Regulatory |
| 55 | MTHFR deficiency | Pro572Leu | c.1715C>T | Missense | Exon 10 | Regulatory |
| 56 | MTHFR deficiency | Val575Gly | c.1724T>G | Missense | Exon 10 | Regulatory |
| 57 | MTHFR deficiency | Met581Ile | c.1743G>A | Missense | Exon 10 | Regulatory |
| 58 | MTHFR deficiency | Lys584* | c.1750A>T | Non-sense | Exon 10 | Regulatory |
| 59 | MTHFR deficiency | Leu598Pro | c.1793T>C | Missense | Exon 11 | Regulatory |
| 60 | MTHFR deficiency | Leu628Pro | c.1883T>C | Missense | Exon 11 | Regulatory |
| 61 | MTHFR deficiency | *657Arg | c.1969T>C | Stop loss | Exon 11 | Regulatory |
| 62 | MTHFR deficiency | *657Ser | c.1970G>C | Stop loss | Exon 11 | Regulatory |
| 63 | MTHFR deficiency | – | c.236+1G>A | Splice | Intron 2 | Catalytic |
| 64 | MTHFR deficiency | – | c.474A>T | Splice | Exon 2 | Catalytic |
| 65 | MTHFR deficiency | – | c.781-2A>G | Splice | Intron 5 | Catalytic |
| 66 | MTHFR deficiency | – | c.781-1G>A | Splice | Intron 5 | Catalytic |
| 67 | MTHFR deficiency | – | c.780+1G>T | Splice | Intron 5 | Catalytic |
| 68 | MTHFR deficiency | – | c.1166G>A | Splice | Exon 6 | Catalytic |
| 69 | MTHFR deficiency | – | c.1166+1G>A | Splice | Intron 7 | Catalytic |
| 70 | MTHFR deficiency | – | c.1347+1G>A | Splice | Intron 8 | Regulatory |
| 71 | MTHFR deficiency | – | c.1530+2T>C | Splice | Intron 9 | Regulatory |
| 72 | MTHFR deficiency | – | c.1632+2T>G | Splice | Intron 10 | Regulatory |
| 73 | MTHFR deficiency | – | c.1753-18G>A | Splice | Intron 10 | Regulatory |
| 74 | MTHFR deficiency | – | c.1752+1G>T | Splice | Intron 11 | Regulatory |
| 75 | MTHFR deficiency | – | c.643_645delAAG | Small deletions | Exon 4 | |
| 76 | MTHFR deficiency | – | c.-40_-41delTC | Small deletions 5′UTR | Intron 1 | Serine rich |
| 77 | MTHFR deficiency | – | c.662delG | Small deletions | Exon 4 | Catalytic |
| 78 | MTHFR deficiency | – | c.677_679delTCA | Small deletions | Exon 4 | Catalytic |
| 79 | MTHFR deficiency | – | c.1167-2delA | Small deletions | Exon 7 | Regulatory |
| 80 | MTHFR deficiency | – | c.1593delG | Small deletions | Exon 9 | Regulatory |
| 81 | MTHFR deficiency | – | c.1539dupA | Small deletions | Exon 9 | Regulatory |
| 82 | MTHFR deficiency | – | c.446_447delGCinsTT | Small indels | Exon 2 | Catalytic |
| 83 | MTHFR deficiency | – | c.1797_1808delins12 | Small indels | Exon 11 | Regulatory |
| 84 | MTHFR deficiency | Leu89_Pro101dup | c.276_314dup | Gross insertions | Exon 2 | Catalytic |