Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19910 | 59953;59954;59955 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| N2AB | 18269 | 55030;55031;55032 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| N2A | 17342 | 52249;52250;52251 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| N2B | 10845 | 32758;32759;32760 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| Novex-1 | 10970 | 33133;33134;33135 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| Novex-2 | 11037 | 33334;33335;33336 | chr2:178592176;178592175;178592174 | chr2:179456903;179456902;179456901 |
| 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/I | rs369476725  |
0.042 | 1.0 | N | 0.779 | 0.454 | None | gnomAD-2.1.1 | 1.49853E-04 | None | None | None | None | I | None | 0 | 5.83E-05 | None | 1.9988E-03 | 0 | None | 3.28E-05 | None | 0 | 8.96E-05 | 6.69568E-04 |
| T/I | rs369476725 |
0.042 | 1.0 | N | 0.779 | 0.454 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 1.44175E-03 | 0 | None | 0 | 0 | 1.17689E-04 | 0 | 4.78469E-04 |
| T/I | rs369476725 |
0.042 | 1.0 | N | 0.779 | 0.454 | None | gnomAD-4.0.0 | 7.75146E-05 | None | None | None | None | I | None | 0 | 3.33968E-05 | None | 2.02826E-03 | 0 | None | 0 | 4.93908E-04 | 3.22188E-05 | 1.09902E-05 | 3.36571E-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 | 0.1317 | likely_benign | 0.1391 | benign | -0.696 | Destabilizing | 0.996 | D | 0.444 | neutral | N | 0.492274651 | None | None | I |
| T/C | 0.5293 | ambiguous | 0.522 | ambiguous | -0.453 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| T/D | 0.6784 | likely_pathogenic | 0.7387 | pathogenic | -0.436 | Destabilizing | 0.994 | D | 0.635 | neutral | None | None | None | None | I |
| T/E | 0.5193 | ambiguous | 0.6021 | pathogenic | -0.465 | Destabilizing | 0.91 | D | 0.315 | neutral | None | None | None | None | I |
| T/F | 0.4412 | ambiguous | 0.4643 | ambiguous | -0.905 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| T/G | 0.2943 | likely_benign | 0.3033 | benign | -0.917 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| T/H | 0.3811 | ambiguous | 0.4143 | ambiguous | -1.275 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| T/I | 0.3256 | likely_benign | 0.3705 | ambiguous | -0.209 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.49731967 | None | None | I |
| T/K | 0.3305 | likely_benign | 0.4004 | ambiguous | -0.757 | Destabilizing | 0.997 | D | 0.672 | neutral | None | None | None | None | I |
| T/L | 0.1318 | likely_benign | 0.1555 | benign | -0.209 | Destabilizing | 0.998 | D | 0.627 | neutral | None | None | None | None | I |
| T/M | 0.1232 | likely_benign | 0.1276 | benign | 0.172 | Stabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| T/N | 0.1877 | likely_benign | 0.1975 | benign | -0.663 | Destabilizing | 0.999 | D | 0.674 | neutral | D | 0.526141067 | None | None | I |
| T/P | 0.6014 | likely_pathogenic | 0.6347 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.523674222 | None | None | I |
| T/Q | 0.2982 | likely_benign | 0.3346 | benign | -0.911 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | I |
| T/R | 0.3024 | likely_benign | 0.3671 | ambiguous | -0.454 | Destabilizing | 0.999 | D | 0.778 | deleterious | None | None | None | None | I |
| T/S | 0.129 | likely_benign | 0.1273 | benign | -0.878 | Destabilizing | 0.996 | D | 0.421 | neutral | N | 0.464495175 | None | None | I |
| T/V | 0.236 | likely_benign | 0.257 | benign | -0.34 | Destabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | I |
| T/W | 0.762 | likely_pathogenic | 0.7959 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| T/Y | 0.4814 | ambiguous | 0.5303 | ambiguous | -0.609 | Destabilizing | 1.0 | D | 0.797 | deleterious | 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.