Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29353 | 88282;88283;88284 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| N2AB | 27712 | 83359;83360;83361 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| N2A | 26785 | 80578;80579;80580 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| N2B | 20288 | 61087;61088;61089 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| Novex-1 | 20413 | 61462;61463;61464 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| Novex-2 | 20480 | 61663;61664;61665 | chr2:178557097;178557096;178557095 | chr2:179421824;179421823;179421822 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs1311421658  |
-0.513 | None | N | 0.488 | 0.18 | 0.31501682445 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| S/R | rs1311421658 |
-0.513 | None | N | 0.488 | 0.18 | 0.31501682445 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/R | rs1311421658 |
-0.513 | None | N | 0.488 | 0.18 | 0.31501682445 | gnomAD-4.0.0 | 9.29609E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.27141E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1066 | likely_benign | 0.0969 | benign | -0.903 | Destabilizing | 0.016 | N | 0.361 | neutral | None | None | None | None | N |
| S/C | 0.0873 | likely_benign | 0.08 | benign | -0.807 | Destabilizing | 0.612 | D | 0.645 | neutral | N | 0.495135033 | None | None | N |
| S/D | 0.4393 | ambiguous | 0.3223 | benign | -0.75 | Destabilizing | 0.038 | N | 0.48 | neutral | None | None | None | None | N |
| S/E | 0.5399 | ambiguous | 0.4461 | ambiguous | -0.658 | Destabilizing | 0.016 | N | 0.438 | neutral | None | None | None | None | N |
| S/F | 0.1958 | likely_benign | 0.1762 | benign | -0.939 | Destabilizing | 0.356 | N | 0.613 | neutral | None | None | None | None | N |
| S/G | 0.1265 | likely_benign | 0.1082 | benign | -1.215 | Destabilizing | 0.012 | N | 0.435 | neutral | N | 0.486323169 | None | None | N |
| S/H | 0.2133 | likely_benign | 0.1649 | benign | -1.588 | Destabilizing | 0.001 | N | 0.478 | neutral | None | None | None | None | N |
| S/I | 0.1422 | likely_benign | 0.1192 | benign | -0.151 | Destabilizing | 0.093 | N | 0.66 | neutral | N | 0.511478259 | None | None | N |
| S/K | 0.5044 | ambiguous | 0.3905 | ambiguous | -0.469 | Destabilizing | 0.016 | N | 0.423 | neutral | None | None | None | None | N |
| S/L | 0.114 | likely_benign | 0.1083 | benign | -0.151 | Destabilizing | 0.038 | N | 0.615 | neutral | None | None | None | None | N |
| S/M | 0.1776 | likely_benign | 0.1658 | benign | -0.115 | Destabilizing | 0.356 | N | 0.648 | neutral | None | None | None | None | N |
| S/N | 0.1138 | likely_benign | 0.09 | benign | -0.772 | Destabilizing | None | N | 0.259 | neutral | N | 0.507437876 | None | None | N |
| S/P | 0.8996 | likely_pathogenic | 0.8607 | pathogenic | -0.368 | Destabilizing | 0.356 | N | 0.706 | prob.neutral | None | None | None | None | N |
| S/Q | 0.3804 | ambiguous | 0.3117 | benign | -0.793 | Destabilizing | 0.072 | N | 0.574 | neutral | None | None | None | None | N |
| S/R | 0.4325 | ambiguous | 0.3346 | benign | -0.566 | Destabilizing | None | N | 0.488 | neutral | N | 0.501261265 | None | None | N |
| S/T | 0.0745 | likely_benign | 0.0719 | benign | -0.672 | Destabilizing | None | N | 0.254 | neutral | N | 0.379758993 | None | None | N |
| S/V | 0.1756 | likely_benign | 0.153 | benign | -0.368 | Destabilizing | 0.038 | N | 0.615 | neutral | None | None | None | None | N |
| S/W | 0.3415 | ambiguous | 0.3106 | benign | -0.967 | Destabilizing | 0.864 | D | 0.655 | neutral | None | None | None | None | N |
| S/Y | 0.1654 | likely_benign | 0.1435 | benign | -0.624 | Destabilizing | 0.12 | N | 0.623 | neutral | None | None | None | None | N |
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.