Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24038 | 72337;72338;72339 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| N2AB | 22397 | 67414;67415;67416 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| N2A | 21470 | 64633;64634;64635 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| N2B | 14973 | 45142;45143;45144 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| Novex-1 | 15098 | 45517;45518;45519 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| Novex-2 | 15165 | 45718;45719;45720 | chr2:178574020;178574019;178574018 | chr2:179438747;179438746;179438745 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs370375696  |
-0.088 | 0.973 | N | 0.389 | 0.258 | None | gnomAD-2.1.1 | 1.35913E-03 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 1.20962E-02 | None | 4E-05 | 2.35E-05 | 4.22178E-04 |
| T/M | rs370375696 |
-0.088 | 0.973 | N | 0.389 | 0.258 | None | gnomAD-3.1.2 | 3.09231E-04 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 1.88857E-04 | 0 | 2.94E-05 | 8.28157E-03 | 0 |
| T/M | rs370375696 |
-0.088 | 0.973 | N | 0.389 | 0.258 | None | 1000 genomes | 1.99681E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.02E-02 | None |
| T/M | rs370375696 |
-0.088 | 0.973 | N | 0.389 | 0.258 | None | gnomAD-4.0.0 | 6.6572E-04 | None | None | None | None | N | None | 4.00203E-05 | 1.66744E-05 | None | 0 | 2.23764E-05 | None | 3.12588E-05 | 0 | 1.78028E-05 | 1.0992E-02 | 7.20369E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.077 | likely_benign | 0.0825 | benign | -0.645 | Destabilizing | 0.27 | N | 0.347 | neutral | N | 0.45312122 | None | None | N |
| T/C | 0.3782 | ambiguous | 0.4204 | ambiguous | -0.401 | Destabilizing | 0.995 | D | 0.373 | neutral | None | None | None | None | N |
| T/D | 0.3695 | ambiguous | 0.3868 | ambiguous | 0.174 | Stabilizing | 0.543 | D | 0.419 | neutral | None | None | None | None | N |
| T/E | 0.3034 | likely_benign | 0.3203 | benign | 0.12 | Stabilizing | 0.704 | D | 0.418 | neutral | None | None | None | None | N |
| T/F | 0.2494 | likely_benign | 0.2904 | benign | -1.01 | Destabilizing | 0.893 | D | 0.495 | neutral | None | None | None | None | N |
| T/G | 0.247 | likely_benign | 0.2614 | benign | -0.817 | Destabilizing | 0.495 | N | 0.46 | neutral | None | None | None | None | N |
| T/H | 0.3091 | likely_benign | 0.3224 | benign | -1.161 | Destabilizing | 0.944 | D | 0.457 | neutral | None | None | None | None | N |
| T/I | 0.112 | likely_benign | 0.1281 | benign | -0.302 | Destabilizing | 0.007 | N | 0.251 | neutral | None | None | None | None | N |
| T/K | 0.2479 | likely_benign | 0.2664 | benign | -0.534 | Destabilizing | 0.82 | D | 0.414 | neutral | N | 0.507309298 | None | None | N |
| T/L | 0.0957 | likely_benign | 0.1064 | benign | -0.302 | Destabilizing | 0.329 | N | 0.385 | neutral | None | None | None | None | N |
| T/M | 0.0852 | likely_benign | 0.078 | benign | -0.03 | Destabilizing | 0.973 | D | 0.389 | neutral | N | 0.492154114 | None | None | N |
| T/N | 0.1278 | likely_benign | 0.1309 | benign | -0.333 | Destabilizing | 0.013 | N | 0.14 | neutral | None | None | None | None | N |
| T/P | 0.2006 | likely_benign | 0.2052 | benign | -0.386 | Destabilizing | 0.927 | D | 0.434 | neutral | N | 0.508501376 | None | None | N |
| T/Q | 0.2786 | likely_benign | 0.2929 | benign | -0.557 | Destabilizing | 0.944 | D | 0.421 | neutral | None | None | None | None | N |
| T/R | 0.2081 | likely_benign | 0.2253 | benign | -0.295 | Destabilizing | 0.97 | D | 0.433 | neutral | N | 0.509541526 | None | None | N |
| T/S | 0.1222 | likely_benign | 0.1276 | benign | -0.607 | Destabilizing | 0.065 | N | 0.223 | neutral | N | 0.4763116 | None | None | N |
| T/V | 0.0878 | likely_benign | 0.0976 | benign | -0.386 | Destabilizing | 0.013 | N | 0.143 | neutral | None | None | None | None | N |
| T/W | 0.6519 | likely_pathogenic | 0.6709 | pathogenic | -0.947 | Destabilizing | 0.995 | D | 0.496 | neutral | None | None | None | None | N |
| T/Y | 0.3027 | likely_benign | 0.3195 | benign | -0.699 | Destabilizing | 0.981 | D | 0.484 | 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.