Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35363 | 106312;106313;106314 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| N2AB | 33722 | 101389;101390;101391 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| N2A | 32795 | 98608;98609;98610 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| N2B | 26298 | 79117;79118;79119 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| Novex-1 | 26423 | 79492;79493;79494 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| Novex-2 | 26490 | 79693;79694;79695 | chr2:178530528;178530527;178530526 | chr2:179395255;179395254;179395253 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | None | None | 0.124 | N | 0.621 | 0.048 | 0.0884992946249 | gnomAD-4.0.0 | 1.59091E-06 | None | None | None | None | I | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/R | rs1575217507  |
None | 0.497 | N | 0.692 | 0.052 | 0.250579442822 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/R | rs1575217507 |
None | 0.497 | N | 0.692 | 0.052 | 0.250579442822 | gnomAD-4.0.0 | 1.31458E-05 | None | None | None | None | I | None | 4.82835E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.1157 | likely_benign | 0.1183 | benign | -0.374 | Destabilizing | 0.001 | N | 0.289 | neutral | N | 0.436279234 | None | None | I |
| G/C | 0.1991 | likely_benign | 0.2071 | benign | -0.869 | Destabilizing | 0.883 | D | 0.728 | prob.delet. | N | 0.437039703 | None | None | I |
| G/D | 0.3174 | likely_benign | 0.2815 | benign | -0.563 | Destabilizing | 0.124 | N | 0.621 | neutral | N | 0.445094898 | None | None | I |
| G/E | 0.3489 | ambiguous | 0.3197 | benign | -0.715 | Destabilizing | 0.157 | N | 0.649 | neutral | None | None | None | None | I |
| G/F | 0.648 | likely_pathogenic | 0.6451 | pathogenic | -1.108 | Destabilizing | 0.726 | D | 0.734 | prob.delet. | None | None | None | None | I |
| G/H | 0.5158 | ambiguous | 0.4976 | ambiguous | -0.716 | Destabilizing | 0.909 | D | 0.695 | prob.neutral | None | None | None | None | I |
| G/I | 0.3623 | ambiguous | 0.3754 | ambiguous | -0.428 | Destabilizing | 0.567 | D | 0.728 | prob.delet. | None | None | None | None | I |
| G/K | 0.6104 | likely_pathogenic | 0.5946 | pathogenic | -0.736 | Destabilizing | 0.157 | N | 0.655 | neutral | None | None | None | None | I |
| G/L | 0.4194 | ambiguous | 0.4231 | ambiguous | -0.428 | Destabilizing | 0.567 | D | 0.697 | prob.neutral | None | None | None | None | I |
| G/M | 0.5086 | ambiguous | 0.5178 | ambiguous | -0.354 | Destabilizing | 0.968 | D | 0.733 | prob.delet. | None | None | None | None | I |
| G/N | 0.3453 | ambiguous | 0.3313 | benign | -0.37 | Destabilizing | 0.396 | N | 0.592 | neutral | None | None | None | None | I |
| G/P | 0.9138 | likely_pathogenic | 0.9169 | pathogenic | -0.376 | Destabilizing | 0.003 | N | 0.398 | neutral | None | None | None | None | I |
| G/Q | 0.4599 | ambiguous | 0.4465 | ambiguous | -0.68 | Destabilizing | 0.567 | D | 0.695 | prob.neutral | None | None | None | None | I |
| G/R | 0.3981 | ambiguous | 0.4282 | ambiguous | -0.362 | Destabilizing | 0.497 | N | 0.692 | prob.neutral | N | 0.493830208 | None | None | I |
| G/S | 0.0701 | likely_benign | 0.0719 | benign | -0.565 | Destabilizing | None | N | 0.247 | neutral | N | 0.422660756 | None | None | I |
| G/T | 0.1485 | likely_benign | 0.152 | benign | -0.648 | Destabilizing | 0.157 | N | 0.616 | neutral | None | None | None | None | I |
| G/V | 0.2313 | likely_benign | 0.2461 | benign | -0.376 | Destabilizing | 0.331 | N | 0.704 | prob.neutral | N | 0.494176924 | None | None | I |
| G/W | 0.5073 | ambiguous | 0.4734 | ambiguous | -1.258 | Destabilizing | 0.968 | D | 0.686 | prob.neutral | None | None | None | None | I |
| G/Y | 0.5507 | ambiguous | 0.5263 | ambiguous | -0.884 | Destabilizing | 0.726 | D | 0.734 | prob.delet. | None | None | 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.