Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23793 | 71602;71603;71604 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| N2AB | 22152 | 66679;66680;66681 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| N2A | 21225 | 63898;63899;63900 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| N2B | 14728 | 44407;44408;44409 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| Novex-1 | 14853 | 44782;44783;44784 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| Novex-2 | 14920 | 44983;44984;44985 | chr2:178574755;178574754;178574753 | chr2:179439482;179439481;179439480 |
| 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/A | None | None | 0.349 | N | 0.401 | 0.131 | 0.151104730317 | gnomAD-4.0.0 | 1.36947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9997E-07 | 0 | 1.65826E-05 |
| T/S | rs1709465876  |
None | 0.722 | N | 0.403 | 0.151 | 0.195762928549 | gnomAD-4.0.0 | 1.36947E-06 | None | None | None | None | N | None | 5.97872E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0795 | likely_benign | 0.0777 | benign | -0.968 | Destabilizing | 0.349 | N | 0.401 | neutral | N | 0.462220087 | None | None | N |
| T/C | 0.4501 | ambiguous | 0.4348 | ambiguous | -0.538 | Destabilizing | 0.996 | D | 0.464 | neutral | None | None | None | None | N |
| T/D | 0.5874 | likely_pathogenic | 0.5709 | pathogenic | -0.161 | Destabilizing | 0.775 | D | 0.392 | neutral | None | None | None | None | N |
| T/E | 0.4113 | ambiguous | 0.3944 | ambiguous | -0.195 | Destabilizing | 0.775 | D | 0.417 | neutral | None | None | None | None | N |
| T/F | 0.4565 | ambiguous | 0.4431 | ambiguous | -1.259 | Destabilizing | 0.987 | D | 0.537 | neutral | None | None | None | None | N |
| T/G | 0.2973 | likely_benign | 0.2841 | benign | -1.168 | Destabilizing | 0.011 | N | 0.236 | neutral | None | None | None | None | N |
| T/H | 0.3412 | ambiguous | 0.3207 | benign | -1.475 | Destabilizing | 0.996 | D | 0.531 | neutral | None | None | None | None | N |
| T/I | 0.2967 | likely_benign | 0.2804 | benign | -0.535 | Destabilizing | 0.949 | D | 0.429 | neutral | N | 0.505397648 | None | None | N |
| T/K | 0.2372 | likely_benign | 0.2287 | benign | -0.696 | Destabilizing | 0.044 | N | 0.249 | neutral | None | None | None | None | N |
| T/L | 0.1545 | likely_benign | 0.1463 | benign | -0.535 | Destabilizing | 0.775 | D | 0.421 | neutral | None | None | None | None | N |
| T/M | 0.1082 | likely_benign | 0.1027 | benign | -0.073 | Destabilizing | 0.996 | D | 0.453 | neutral | None | None | None | None | N |
| T/N | 0.1814 | likely_benign | 0.1745 | benign | -0.559 | Destabilizing | 0.901 | D | 0.422 | neutral | N | 0.429283736 | None | None | N |
| T/P | 0.0995 | likely_benign | 0.09 | benign | -0.65 | Destabilizing | 0.008 | N | 0.243 | neutral | N | 0.381553213 | None | None | N |
| T/Q | 0.2578 | likely_benign | 0.2418 | benign | -0.825 | Destabilizing | 0.923 | D | 0.439 | neutral | None | None | None | None | N |
| T/R | 0.2033 | likely_benign | 0.1976 | benign | -0.39 | Destabilizing | 0.858 | D | 0.417 | neutral | None | None | None | None | N |
| T/S | 0.1349 | likely_benign | 0.1334 | benign | -0.87 | Destabilizing | 0.722 | D | 0.403 | neutral | N | 0.465473823 | None | None | N |
| T/V | 0.1803 | likely_benign | 0.1753 | benign | -0.65 | Destabilizing | 0.775 | D | 0.426 | neutral | None | None | None | None | N |
| T/W | 0.7738 | likely_pathogenic | 0.7572 | pathogenic | -1.134 | Destabilizing | 0.996 | D | 0.582 | neutral | None | None | None | None | N |
| T/Y | 0.4673 | ambiguous | 0.4428 | ambiguous | -0.915 | Destabilizing | 0.987 | D | 0.533 | 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.