Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24014 | 72265;72266;72267 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| N2AB | 22373 | 67342;67343;67344 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| N2A | 21446 | 64561;64562;64563 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| N2B | 14949 | 45070;45071;45072 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| Novex-1 | 15074 | 45445;45446;45447 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| Novex-2 | 15141 | 45646;45647;45648 | chr2:178574092;178574091;178574090 | chr2:179438819;179438818;179438817 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.933 | N | 0.729 | 0.235 | 0.415690173769 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs754034457  |
-1.691 | 0.051 | N | 0.275 | 0.153 | 0.0954503805726 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs754034457 |
-1.691 | 0.051 | N | 0.275 | 0.153 | 0.0954503805726 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/S | rs754034457 |
-1.691 | 0.051 | N | 0.275 | 0.153 | 0.0954503805726 | gnomAD-4.0.0 | 2.60331E-05 | None | None | None | None | N | None | 0 | 1.66739E-05 | None | 0 | 0 | None | 0 | 0 | 3.39105E-05 | 0 | 1.60123E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0783 | likely_benign | 0.0782 | benign | -1.779 | Destabilizing | 0.451 | N | 0.488 | neutral | N | 0.472735364 | None | None | N |
| P/C | 0.492 | ambiguous | 0.5224 | ambiguous | -1.098 | Destabilizing | 0.998 | D | 0.801 | deleterious | None | None | None | None | N |
| P/D | 0.6533 | likely_pathogenic | 0.6925 | pathogenic | -1.783 | Destabilizing | 0.841 | D | 0.551 | neutral | None | None | None | None | N |
| P/E | 0.4529 | ambiguous | 0.4845 | ambiguous | -1.755 | Destabilizing | 0.725 | D | 0.483 | neutral | None | None | None | None | N |
| P/F | 0.558 | ambiguous | 0.612 | pathogenic | -1.362 | Destabilizing | 0.998 | D | 0.774 | deleterious | None | None | None | None | N |
| P/G | 0.3978 | ambiguous | 0.4038 | ambiguous | -2.129 | Highly Destabilizing | 0.725 | D | 0.601 | neutral | None | None | None | None | N |
| P/H | 0.2969 | likely_benign | 0.3414 | ambiguous | -1.653 | Destabilizing | 0.993 | D | 0.704 | prob.delet. | None | None | None | None | N |
| P/I | 0.2776 | likely_benign | 0.2865 | benign | -0.891 | Destabilizing | 0.974 | D | 0.791 | deleterious | None | None | None | None | N |
| P/K | 0.4239 | ambiguous | 0.4282 | ambiguous | -1.333 | Destabilizing | 0.725 | D | 0.541 | neutral | None | None | None | None | N |
| P/L | 0.156 | likely_benign | 0.1738 | benign | -0.891 | Destabilizing | 0.933 | D | 0.729 | deleterious | N | 0.475332952 | None | None | N |
| P/M | 0.3675 | ambiguous | 0.3798 | ambiguous | -0.642 | Destabilizing | 0.998 | D | 0.704 | prob.delet. | None | None | None | None | N |
| P/N | 0.4558 | ambiguous | 0.4706 | ambiguous | -1.163 | Destabilizing | 0.949 | D | 0.617 | neutral | None | None | None | None | N |
| P/Q | 0.2545 | likely_benign | 0.2706 | benign | -1.332 | Destabilizing | 0.264 | N | 0.367 | neutral | N | 0.454401894 | None | None | N |
| P/R | 0.3043 | likely_benign | 0.3302 | benign | -0.817 | Destabilizing | 0.933 | D | 0.685 | prob.delet. | N | 0.491584682 | None | None | N |
| P/S | 0.1461 | likely_benign | 0.1554 | benign | -1.706 | Destabilizing | 0.051 | N | 0.275 | neutral | N | 0.404299573 | None | None | N |
| P/T | 0.1251 | likely_benign | 0.1328 | benign | -1.572 | Destabilizing | 0.666 | D | 0.533 | neutral | N | 0.478679902 | None | None | N |
| P/V | 0.2059 | likely_benign | 0.2065 | benign | -1.154 | Destabilizing | 0.949 | D | 0.623 | neutral | None | None | None | None | N |
| P/W | 0.7774 | likely_pathogenic | 0.8174 | pathogenic | -1.589 | Destabilizing | 0.998 | D | 0.739 | deleterious | None | None | None | None | N |
| P/Y | 0.5487 | ambiguous | 0.5943 | pathogenic | -1.302 | Destabilizing | 0.991 | D | 0.789 | deleterious | 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.