Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27223 | 81892;81893;81894 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| N2AB | 25582 | 76969;76970;76971 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| N2A | 24655 | 74188;74189;74190 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| N2B | 18158 | 54697;54698;54699 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| Novex-1 | 18283 | 55072;55073;55074 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| Novex-2 | 18350 | 55273;55274;55275 | chr2:178564465;178564464;178564463 | chr2:179429192;179429191;179429190 |
| 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 | rs755648922  |
-0.168 | 1.0 | N | 0.631 | 0.419 | 0.443999229985 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.13E-06 | 0 |
| T/I | rs755648922 |
-0.168 | 1.0 | N | 0.631 | 0.419 | 0.443999229985 | gnomAD-4.0.0 | 6.16495E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30097E-06 | 0 | 3.31719E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1908 | likely_benign | 0.1831 | benign | -0.237 | Destabilizing | 0.999 | D | 0.491 | neutral | N | 0.480272704 | None | None | I |
| T/C | 0.7403 | likely_pathogenic | 0.7431 | pathogenic | -0.398 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | I |
| T/D | 0.851 | likely_pathogenic | 0.8552 | pathogenic | 0.313 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | I |
| T/E | 0.805 | likely_pathogenic | 0.7982 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| T/F | 0.7592 | likely_pathogenic | 0.722 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| T/G | 0.4777 | ambiguous | 0.477 | ambiguous | -0.312 | Destabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | I |
| T/H | 0.6605 | likely_pathogenic | 0.6687 | pathogenic | -0.492 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| T/I | 0.6413 | likely_pathogenic | 0.5842 | pathogenic | -0.163 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.513422486 | None | None | I |
| T/K | 0.6961 | likely_pathogenic | 0.6759 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| T/L | 0.3277 | likely_benign | 0.2998 | benign | -0.163 | Destabilizing | 0.999 | D | 0.577 | neutral | None | None | None | None | I |
| T/M | 0.2577 | likely_benign | 0.2306 | benign | -0.22 | Destabilizing | 1.0 | D | 0.6 | neutral | None | None | None | None | I |
| T/N | 0.3224 | likely_benign | 0.3594 | ambiguous | -0.122 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.467165276 | None | None | I |
| T/P | 0.6872 | likely_pathogenic | 0.6536 | pathogenic | -0.162 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.482577414 | None | None | I |
| T/Q | 0.5486 | ambiguous | 0.5528 | ambiguous | -0.27 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| T/R | 0.5956 | likely_pathogenic | 0.5673 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | I |
| T/S | 0.2036 | likely_benign | 0.2066 | benign | -0.305 | Destabilizing | 0.999 | D | 0.505 | neutral | N | 0.463030951 | None | None | I |
| T/V | 0.4492 | ambiguous | 0.4086 | ambiguous | -0.162 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | I |
| T/W | 0.9324 | likely_pathogenic | 0.9254 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| T/Y | 0.7735 | likely_pathogenic | 0.7618 | pathogenic | -0.633 | Destabilizing | 1.0 | D | 0.659 | neutral | 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.