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. 2022 Mar 18;13(3):537. doi: 10.3390/genes13030537

Table 1.

SOD1 variants in Amyotrophic Lateral Sclerosis: Systematic re-evaluation according to ACMG-AMP guidelines.

Coding Change (NM_000454.5) Protein Change (NP_000445.1) Variant ID Type PS4 PM3 PP4 PM1 PM2 PP2 PM4 PM5 PM6 PP1 PP3 PP5 PS1 PS2 PS3 PVS1 Benign Criteria Re-Classification
c.13G>A p.Ala5Thr rs121912444 Missense variant *M X X X X X *S P
c.13G>T p.Ala5Ser rs121912444 Missense variant *M X X X X X P
c.13_14delGCinsTT p.Ala5Phe Missense variant *M X X X X LP
c.14C>T p.Ala5Val rs121912442 Missense variant *M X X X X X *S P
c.16G>T p.Val6Leu rs1568807314 Missense variant *M X X X X LP
c.19T>A p.Cys7Ser rs1312702973 Missense variant *M X X X X LP
c.19T>G p.Cys7Gly rs1312702973 Missense variant *M X X X X LP
c.20G>A p.Cys7Tyr rs121912448 Missense variant *M X X X X LP
c.21C>G p.Cys7Trp Missense variant *M X X X X LP
c.23T>A p.Val8Glu rs1568807330 Missense variant *M X X X X LP
c.25C>G p.Leu9Val rs1568807333 Missense variant *S X X X X X P
c.26T>A p.Leu9Gln rs1568807342 Missense variant *S X X X X X P
c.31G>C p.Gly11Arg rs1568807350 Missense variant *S X X X LP
c.32G>C p.Gly11Ala rs1555836167 Missense variant *S X X X LP
c.34G>T p.Asp12Tyr rs762628133 Missense variant *S X X X LP
c.35A>C p.Asp12Ala rs1568807374 Missense variant *S X X VUS
c.37G>C p.Gly13Arg rs121912456 Missense variant *M X X X X LP
c.43G>A p.Val15*Met rs1568807400 Missense variant *M X X X X X *M LP
c.44T>C p.Val15Ala rs1202989817 Missense variant *M X X X LP
c.44T>G p.Val15Gly rs1202989817 Missense variant *M X X X X *M LP
c.49G>A p.Gly17Ser rs121912453 Missense variant *M X X X X X LP
c.50G>C p.Gly17Ala rs1200906022 Missense variant *M X X X X X LP
c.358-304C>G rs1555836889 intron variant X VUS
c.56_58delTCA p.Ile19del frameshift variant *M X X X LP
c.59A>G p.Asn20Ser rs768029813 Missense variant *M X X VUS
c.62T>G p.Phe21Cys rs1555836169 Missense variant *M X X X X LP
c.63C>G p.Phe21Leu rs1555836170 Missense variant *M X X X X LP
c.64G>A p.Glu22Lys rs121912450 Missense variant *M X X X X *M LP
c.65A>G p.Glu22Gly rs1568807435 Missense variant *M X X X X *M LP
c.66G>C p.Glu22Asp Missense variant *M X X X X LP
c.68A>T p.Gln23Leu rs1169198442 Missense variant *M X X X X LP
c.68A>G p.Gln23Arg rs1169198442 Missense variant *M X X X X LP
c.69G>C p.Gln23His rs1424217272 Missense variant *M X X X X LP
c.89T>C p.Val30Ala rs1568809118 Missense variant X X X VUS
c.95T>C p.Val32Ala rs1428716759 Missense variant *H X X X X LP
c.95T>G p.Val32Gly rs1428716759 Missense variant *H X X X X LP
c.112G>A p.Gly38Arg rs121912431 Missense variant *M X X X X X *S P
c.112G>C p.Gly38Arg rs121912431 Missense variant *M X X X X X *S P
c.113G>T p.Gly38Val rs1555836517 Missense variant *M X X X X LP
c.115C>G p.Leu39Val rs121912432 Missense variant *M X X X X X LP
c.116T>A p.Leu39Gln rs1555836520 Missense variant *M X X X X LP
c.116T>G p.Leu39Arg rs1555836520 Missense variant *M X X X X *H LP
c.116T>C p.Leu39Pro Missense variant *M X X X X LP
c.122A>G p.Glu41Gly rs1568809149 Missense variant *M X X X LP
c.123A>T p.Glu41Asp Missense variant *M X X X LP
c.124G>A p.Gly42Ser rs121912433 Missense variant *M X X X X X *M LP
c.125G>A p.Gly42Asp rs121912434 Missense variant *M X X X X X *M LP
c.131A>G p.His44Arg rs121912435 Missense variant *M X X X X LP
c.137T>C p.Phe46Ser rs121912457 Missense variant *M X X X X LP
c.137T>G p.Phe46Cys rs121912457 Missense variant *M X X X X LP
c.139C>G p.His47Asp rs748897491 Missense variant *M X X X X LP
c.140A>G p.His47Arg rs121912443 Missense variant *M X X X X *S P
c.142G>T p.Val48Phe rs1555836523 Missense variant *M X X X LP
c.143T>C p.Val48Ala rs1568809169 Missense variant *M X X X LP
c.146A>G p.His49Arg rs1568809172 Missense variant *M X X X X X LP
c.147T>G p.His49Gln rs1568809175 Missense variant *M X X X X X LP
c.148G>A p.Glu50Lys rs1568809178 Missense variant *M X X X LP
c.164C>G p.Thr55Arg rs986277034 Missense variant *H X X X X LP
c.172T>C p.Cys58Arg rs1568810255 Missense variant *H X X X VUS
c.172T>G p.Cys58Gly Missense variant *H X X X VUS
c.179G>A p.Ser60Asn rs1413388444 Missense variant *H X X X VUS
c.179G>T p.Ser60Ile rs1413388444 Missense variant *H X X X VUS
c.184G>C p.Gly62Arg rs1568810268 Missense variant *M X X X LP
c.193T>C p.Phe65Leu rs1030039318 Missense variant *M X X X X LP
c.197A>G p.Asn66Ser rs1568810275 Missense variant *M X X X X LP
c.199C>G p.Pro67Ala rs1356474292 Missense variant *M X X X X LP
c.199C>T p.Pro67Ser rs1356474292 Missense variant *M X X X X LP
c.199G>C p.Pro67Ala rs1356474292 Missense variant *M X X X X LP
c.200C>G p.Pro67Arg rs1568810284 Missense variant *M X X X X LP
c.203T>C p.Leu68Pro rs1568810289 Missense variant *M X X X X BP4 LP
c.203T>G p.Leu68Arg rs1568810289 Missense variant *M X X X LP
c.215A>C p.His72Pro Missense variant *M X X X X LP
c.217G>A p.Gly73Ser rs121912455 Missense variant *M X X X X LP
c.217G>T p.Gly73Cys rs121912455 Missense variant *M X X X X LP
c.218G>A p.Gly73Asp Missense variant *M X X X X LP
c.223C>T p.Pro75Ser Missense variant *M X X X *H LP
c.224C>G p.Pro75Arg Missense variant *M X X X LP
c.229G>T p.Asp77Tyr rs1601157750 Missense variant *H X X X X X LP
c.230A>T p.Asp77Val rs1568810316 Missense variant *H X X X X X LP
c.230A>G p.Asp77Gly Missense variant *H X X X X LP
c.240-7T>G rs1568810602 splice region X X VUS
c.241C>T p.His81Tyr Missense variant *M X X X X LP
c.242A>G p.His81Arg rs121912458 Missense variant *M X X X X X LP
c.250G>A p.Asp84Asn rs1555836789 Missense variant *M X X X LP
c.251A>T p.Asp84Val Missense variant *M X X X LP
c.251A>G p.Asp84Gly rs1568810615 Missense variant *M X X X LP
c.253T>G p.Leu85Val rs121912452 Missense variant *M X X X X X *S BP7 P
c.255G>C p.Leu85Phe rs1315541036 Missense variant *S X X X X X X P
c.255G>T p.Leu85Phe Missense variant *S X X X X X P
c.256G>A p.Gly86Ser rs121912436 synonymous variant *S X X X X X P
c.256G>C p.Gly86Arg rs121912436 Missense variant *S X X X X X *S P
c.259A>G p.Asn87Asp rs1555836792 Missense variant *S X X X X LP
c.260A>G p.Asn87Ser rs11556620 Missense variant *S X X X X *M P
c.260A>T p.Asn87Ile rs11556620 Missense variant *M X X X X LP
c.261T>A p.Asn87Lys rs1555836793 Missense variant *S X X X X P
c.262G>A p.Val88Met rs1568810641 Missense variant *S X X X X X P
c.263T>C p.Val88Ala rs1339283341 Missense variant *S X X X X X P
c.268G>A p.Ala90Thr rs1568810660 Missense variant *S X X X X X P
c.269C>T p.Ala90Val rs1280042397 Missense variant *S X X X X X P
c.271G>A p.Asp91Asn rs1343616996 Missense variant *S X X X BP4 LP
c.272A>C p.Asp91Ala rs80265967 Missense variant *S X X X X *S P
c.272A>T p.Asp91Val rs80265967 Missense variant *S X X X P
c.272_274dupACA p.Asp91_Lys92
insAsn		 frameshift variant *S X X LP
c.275_276delAA p.Lys92ArgfsTer9 frameshift variant X *S P
c.280G>A p.Gly94Ser rs121912437 Missense variant *S X X X X *M P
c.280G>T p.Gly94Cys rs121912437 Missense variant *S X X X X X P
c.280G>C p.Gly94Arg rs121912437 Missense variant *S X X X X X *S P
c.281G>A p.Gly94Asp rs121912438 Missense variant *S X X X X X *M P
c.281G>C p.Gly94Ala rs121912438 Missense variant *S X X X X X *S P
c.284T>C p.Val95Ala rs202198235 Missense variant *S X X X LP
c.286G>A p.Ala96Thr rs1568810686 Missense variant *S X X X X LP
c.287C>G p.Ala96Gly rs1568810690 Missense variant *S X X X X LP
c.287C>T p.Ala96Val rs1568810690 Missense variant *S X X X X LP
c.289G>A p.Asp97Asn rs121912459 Missense variant *S X X X BP4 LP
c.290A>T p.Asp97Val rs1555836803 Missense variant *S X X X BP4 LP
c.292G>A p.Val98*Met rs1555836806 Missense variant *S X X X X LP
c.292G>C p.Val98Leu rs1555836806 Missense variant *S X X X X LP
c.298A>G p.Ile100Val rs760740095 Missense variant *S X X VUS
c.301G>A p.Glu101Lys rs76731700 Missense variant *S X X X X *M P
c.301G>T p.Glu101Ter rs76731700 stop gained X *VS P
c.301G>C p.Glu101Gln Missense variant *S X X X LP
c.302A>G p.Glu101Gly rs121912439 Missense variant *S X X X X X *M P
c.304G>A p.Asp102Asn rs1568810715 Missense variant *S X X X X X P
c.304G>C p.Asp102His rs1568810715 Missense variant *S X X X X X P
c.304G>T p.Asp102Ty rs1568810715 Missense variant *S X X X X LP
c.305A>G p.Asp102Gly rs1568810721 Missense variant *S X X X X X *M P
c.313A>T p.Ile105Phe rs121912445 Missense variant *M X X X X LP
c.317C>T p.Ser106Leu rs1378590183 Missense variant *M X X X X LP
c.319C>G p.Leu107Val rs121912440 Missense variant *S X X X X LP
c.319C>T p.Leu107Phe rs121912440 Missense variant *S X X X X LP
c.320_321insT p.Ser108LeufsTer15 frameshift variant X X *VS P
c.326G>A p.Gly109Glu rs1359299834 Missense variant *S X X X X LP
c.326G>T p.Gly109Val rs1359299834 Missense variant *S X X X X P
c.328G>T p.Asp110Tyr rs567432143 Missense variant *S X X VUS
c.335G>A p.Cys112Tyr rs1601158483 Missense variant *S X X X X LP
c.335dup p.Cys112TrpfsTer11 rs1568810771 frameshift variant X X X *VS P
c.338T>C p.Ile113Thr rs74315452 Missense variant *S X X X X X P
c.339C>G p.Ile113*Met rs1299542356 Missense variant *M X X X X LP
c.340A>T p.Ile114Phe rs1568810780 Missense variant *M X X X X LP
c.341T>C p.Ile114Thr rs121912441 Missense variant *M X X X X *M LP
c.344G>C p.Gly115Ala rs1568810789 Missense variant *M X X X X LP
c.346C>G p.Arg116Gly rs1301635320 Missense variant *M X X X X X LP
c.346C>T p.Arg116Cys rs1301635320 Missense variant *M X X X X LP
c.358-11A>G rs369600566 intron variant X X VUS
c.358-10T>G rs1197141604 intron variant X X VUS
c.350C>G p.Thr117Arg rs1568810800 Missense variant *M X X X LP
c.352C>G p.Leu118Val rs199474723 Missense variant *M X X *M LP
c.355G>C p.Val119Leu rs1235629842 Missense variant *M X X X X X P
c.355G>T p.Val119Leu rs1235629842 Missense variant *M X X X X X LP
c.355G>A p.Val119Met Missense variant *M X X X X LP
c.358G>T p.Val120Phe Missense variant *M X X X LP
c.358G>C p.Val120Leu rs1457889952 Missense variant *M X X X X LP
c.361C>A p.His121Asn Missense variant *M X X X LP
c.362A>T p.His121Leu rs1410925719 Missense variant *M X X X LP
c.374A>C p.Asp125Ala rs1568811366 Missense variant *M X X X X LP
c.374A>T p.Asp125Val rs1568811366 Missense variant *M X X X X X *M LP
c.376G>C p.Asp126His rs1568811372 Missense variant *M X X X X X LP
c.376G>A p.Asp126Asn Missense variant *M X X X X X LP
c.377A>C rs1164911383 Missense variant *M X X X X X LP
c.380T>A p.Leu127Ter rs121912454 stop gained X X X *VS P
c.380T>C p.Leu127Ser rs121912454 Missense variant *M X X X X LP
c.382G>C p.Gly128Arg rs1568811389 Missense variant *M X X X LP
c.383_384insACCC p.Lys129ProfsTer6 frameshift variant X X *VS P
c.383_392dup p.Asn132GlnfsTer5 frameshift variant X X X *VS P
c.384_385insTGGG p.Lys129TrpfsTer6 frameshift variant X X *VS P
c.385A>G p.Lys129Glu Missense variant *M X X X LP
c.400G>A p.Glu134Lys Missense variant *M X X X X LP
c.401A>T p.Glu134Val rs1568811426 Missense variant *M X X X X LP
c.403A>G p.Ser135Gly rs1555836932 Missense variant *M X X X X LP
c.404G>A p.Ser135Asn rs121912451 Missense variant *M X X X X LP
c.404G>C p.Ser135Thr rs121912451 Missense variant *M X X X X LP
c.409A>T p.Lys137Ter rs1555836934 nonsense variant X X *VS P
c.412A>G p.Thr138Ala rs1568811445 Missense variant *M X X X X LP
c.413C>G p.Thr138Arg rs1568811454 Missense variant *M X X X X LP
c.416G>A p.Gly139Glu rs1568811464 Missense variant *M X X X LP
c.418A>C p.Asn140His rs1568811471 Missense variant *S X X X X LP
c.418A>G p.Asn140Asp rs1568811471 Missense variant *S X X X X LP
c.420C>A p.Asn140Lys rs1804449 Missense variant *S X X X X X X *M P
c.422C>G p.Ala141Gly rs1555836937 Missense variant *S X X X LP
c.424G>T p.Gly142Ter rs1319062081 stop gained X X *VS P
c.424G>A p.Gly142Arg Missense variant *S X X X LP
c.425G>A p.Gly142Glu rs1568811489 Missense variant *S X X X LP
c.425G>C p.Gly142Ala rs1568811489 Missense variant *S X X X LP
c.434T>C p.Leu145Ser rs121912446 Missense variant *S X X X X X *M P
c.435G>C p.Leu145Phe rs1482760341 Missense variant *S X X X X X X *M P
c.436G>A p.Ala146Thr rs121912447 Missense variant *S X X X X X P
c.437C>A p.Ala146Asp rs1131690781 Missense variant *S X X X X X P
c.437C>G p.Ala146Gly rs1131690781 Missense variant *S X X X X LP
c.439T>C p.Cys147Arg rs1568811515 Missense variant *S X X X *M P
c.441T>A p.Cys147Ter nonsense variant X X *VS P
c.442G>C p.Gly148Arg rs1568811520 Missense variant *S X X X X X P
c.442G>A p.Gly148Ser Missense variant *S X X X X LP
c.442G>T p.Gly148Cys Missense variant *S X X X X LP
c.443G>A p.Gly148Asp rs1555836950 Missense variant *S X X X X X P
c.445G>A p.Val149Ile rs567511139 Missense variant *M X X X X X LP
c.446T>G p.Val149Gly rs1476760624 Missense variant *M X X X X X *M LP
c.446T>C p.Val149Ala Missense variant *M X X X X LP
c.448A>G p.Ile150Val rs1169917994 Missense variant *M X X X X LP
c.449T>C p.Ile150Thr rs1424014997 Missense variant *M X X X X LP
c.455T>C p.Ile152Thr rs121912449 Missense variant *M X X X X LP
c.455T>G p.Ile152Ser Missense variant *M X X X X LP
c.457G>A p.Ala153Thr rs747094021 Missense variant *M X X X LP

*M = *Moderate, *H = Supporting, *S = Strong, *VS = Very strong. LP = Likely pathogenic, P = Pathogenic, VUS = Variant of uncertain significance.