Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18505 | 55738;55739;55740 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| N2AB | 16864 | 50815;50816;50817 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| N2A | 15937 | 48034;48035;48036 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| N2B | 9440 | 28543;28544;28545 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| Novex-1 | 9565 | 28918;28919;28920 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| Novex-2 | 9632 | 29119;29120;29121 | chr2:178601484;178601483;178601482 | chr2:179466211;179466210;179466209 |
| 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/N | rs563090275  |
0.515 | 0.029 | N | 0.057 | 0.079 | 0.247322355667 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 4.14E-05 | 5.66E-05 | None | 0 | 5.15E-05 | None | 0 | None | 0 | 7.84E-06 | 0 |
| D/N | rs563090275 |
0.515 | 0.029 | N | 0.057 | 0.079 | 0.247322355667 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs563090275 |
0.515 | 0.029 | N | 0.057 | 0.079 | 0.247322355667 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs563090275 |
0.515 | 0.029 | N | 0.057 | 0.079 | 0.247322355667 | gnomAD-4.0.0 | 6.19969E-06 | None | None | None | None | I | None | 2.66745E-05 | 5.0035E-05 | None | 3.38135E-05 | 4.46808E-05 | None | 0 | 0 | 1.69593E-06 | 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 | 0.5144 | ambiguous | 0.508 | ambiguous | -0.192 | Destabilizing | 0.454 | N | 0.344 | neutral | N | 0.495025939 | None | None | I |
| D/C | 0.7097 | likely_pathogenic | 0.7482 | pathogenic | 0.247 | Stabilizing | 0.998 | D | 0.396 | neutral | None | None | None | None | I |
| D/E | 0.3512 | ambiguous | 0.3738 | ambiguous | -0.33 | Destabilizing | 0.809 | D | 0.309 | neutral | N | 0.483366151 | None | None | I |
| D/F | 0.7383 | likely_pathogenic | 0.7987 | pathogenic | -0.347 | Destabilizing | 0.991 | D | 0.42 | neutral | None | None | None | None | I |
| D/G | 0.5884 | likely_pathogenic | 0.5476 | ambiguous | -0.377 | Destabilizing | 0.454 | N | 0.301 | neutral | N | 0.512880981 | None | None | I |
| D/H | 0.5655 | likely_pathogenic | 0.5981 | pathogenic | -0.347 | Destabilizing | 0.986 | D | 0.331 | neutral | N | 0.498066244 | None | None | I |
| D/I | 0.5228 | ambiguous | 0.5742 | pathogenic | 0.238 | Stabilizing | 0.949 | D | 0.442 | neutral | None | None | None | None | I |
| D/K | 0.8366 | likely_pathogenic | 0.8326 | pathogenic | 0.345 | Stabilizing | 0.842 | D | 0.349 | neutral | None | None | None | None | I |
| D/L | 0.6303 | likely_pathogenic | 0.6683 | pathogenic | 0.238 | Stabilizing | 0.842 | D | 0.417 | neutral | None | None | None | None | I |
| D/M | 0.7659 | likely_pathogenic | 0.7955 | pathogenic | 0.493 | Stabilizing | 0.998 | D | 0.393 | neutral | None | None | None | None | I |
| D/N | 0.1271 | likely_benign | 0.1201 | benign | 0.173 | Stabilizing | 0.029 | N | 0.057 | neutral | N | 0.439652659 | None | None | I |
| D/P | 0.983 | likely_pathogenic | 0.9872 | pathogenic | 0.117 | Stabilizing | 0.974 | D | 0.35 | neutral | None | None | None | None | I |
| D/Q | 0.7207 | likely_pathogenic | 0.7363 | pathogenic | 0.191 | Stabilizing | 0.974 | D | 0.337 | neutral | None | None | None | None | I |
| D/R | 0.8345 | likely_pathogenic | 0.838 | pathogenic | 0.379 | Stabilizing | 0.949 | D | 0.409 | neutral | None | None | None | None | I |
| D/S | 0.2821 | likely_benign | 0.2485 | benign | 0.068 | Stabilizing | 0.172 | N | 0.125 | neutral | None | None | None | None | I |
| D/T | 0.4065 | ambiguous | 0.3905 | ambiguous | 0.205 | Stabilizing | 0.067 | N | 0.156 | neutral | None | None | None | None | I |
| D/V | 0.3897 | ambiguous | 0.4236 | ambiguous | 0.117 | Stabilizing | 0.801 | D | 0.432 | neutral | N | 0.510110035 | None | None | I |
| D/W | 0.9466 | likely_pathogenic | 0.9643 | pathogenic | -0.299 | Destabilizing | 0.998 | D | 0.551 | neutral | None | None | None | None | I |
| D/Y | 0.4019 | ambiguous | 0.446 | ambiguous | -0.132 | Destabilizing | 0.996 | D | 0.421 | neutral | N | 0.439615373 | 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.