Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31043 | 93352;93353;93354 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| N2AB | 29402 | 88429;88430;88431 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| N2A | 28475 | 85648;85649;85650 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| N2B | 21978 | 66157;66158;66159 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| Novex-1 | 22103 | 66532;66533;66534 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| Novex-2 | 22170 | 66733;66734;66735 | chr2:178548499;178548498;178548497 | chr2:179413226;179413225;179413224 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs758336721  |
-0.386 | 0.751 | N | 0.205 | 0.266 | 0.134241683229 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs758336721 |
-0.386 | 0.751 | N | 0.205 | 0.266 | 0.134241683229 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs758336721 |
-0.386 | 0.751 | N | 0.205 | 0.266 | 0.134241683229 | gnomAD-4.0.0 | 6.84184E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99446E-07 | 0 | 0 |
| D/G | rs1455870717 |
-0.895 | 0.989 | N | 0.541 | 0.47 | 0.367612772649 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs1455870717 |
-0.895 | 0.989 | N | 0.541 | 0.47 | 0.367612772649 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77269E-05 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.9315 | likely_pathogenic | 0.9057 | pathogenic | -0.477 | Destabilizing | 0.989 | D | 0.556 | neutral | N | 0.509187137 | None | None | I |
| D/C | 0.9891 | likely_pathogenic | 0.9834 | pathogenic | -0.025 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/E | 0.801 | likely_pathogenic | 0.7344 | pathogenic | -0.455 | Destabilizing | 0.751 | D | 0.205 | neutral | N | 0.496816874 | None | None | I |
| D/F | 0.9917 | likely_pathogenic | 0.9888 | pathogenic | -0.316 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| D/G | 0.916 | likely_pathogenic | 0.8972 | pathogenic | -0.749 | Destabilizing | 0.989 | D | 0.541 | neutral | N | 0.518443529 | None | None | I |
| D/H | 0.9551 | likely_pathogenic | 0.9365 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.604 | neutral | D | 0.532824801 | None | None | I |
| D/I | 0.9864 | likely_pathogenic | 0.98 | pathogenic | 0.214 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| D/K | 0.9867 | likely_pathogenic | 0.9793 | pathogenic | 0.047 | Stabilizing | 0.992 | D | 0.545 | neutral | None | None | None | None | I |
| D/L | 0.9748 | likely_pathogenic | 0.9683 | pathogenic | 0.214 | Stabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | I |
| D/M | 0.9943 | likely_pathogenic | 0.9917 | pathogenic | 0.558 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| D/N | 0.5498 | ambiguous | 0.5245 | ambiguous | -0.317 | Destabilizing | 0.733 | D | 0.213 | neutral | N | 0.474055037 | None | None | I |
| D/P | 0.9865 | likely_pathogenic | 0.9848 | pathogenic | 0.007 | Stabilizing | 1.0 | D | 0.602 | neutral | None | None | None | None | I |
| D/Q | 0.9704 | likely_pathogenic | 0.9567 | pathogenic | -0.237 | Destabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | I |
| D/R | 0.9817 | likely_pathogenic | 0.9738 | pathogenic | 0.117 | Stabilizing | 0.998 | D | 0.654 | neutral | None | None | None | None | I |
| D/S | 0.794 | likely_pathogenic | 0.7503 | pathogenic | -0.472 | Destabilizing | 0.992 | D | 0.499 | neutral | None | None | None | None | I |
| D/T | 0.9337 | likely_pathogenic | 0.9093 | pathogenic | -0.251 | Destabilizing | 0.998 | D | 0.544 | neutral | None | None | None | None | I |
| D/V | 0.9606 | likely_pathogenic | 0.945 | pathogenic | 0.007 | Stabilizing | 0.998 | D | 0.68 | prob.neutral | D | 0.528532386 | None | None | I |
| D/W | 0.9977 | likely_pathogenic | 0.9968 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/Y | 0.9317 | likely_pathogenic | 0.9088 | pathogenic | -0.075 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | D | 0.55629788 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.