Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32510 | 97753;97754;97755 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| N2AB | 30869 | 92830;92831;92832 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| N2A | 29942 | 90049;90050;90051 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| N2B | 23445 | 70558;70559;70560 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| Novex-1 | 23570 | 70933;70934;70935 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| Novex-2 | 23637 | 71134;71135;71136 | chr2:178541549;178541548;178541547 | chr2:179406276;179406275;179406274 |
| 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/E | rs375612373  |
-0.037 | 1.0 | N | 0.382 | 0.272 | 0.170165803431 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.55E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs375612373 |
-0.037 | 1.0 | N | 0.382 | 0.272 | 0.170165803431 | gnomAD-4.0.0 | 1.3698E-06 | None | None | None | None | N | None | 5.98229E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs1170311014 |
None | 1.0 | N | 0.726 | 0.557 | 0.27855597813 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs1170311014 |
None | 1.0 | N | 0.726 | 0.557 | 0.27855597813 | gnomAD-4.0.0 | 6.57333E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47042E-05 | 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 | 0.4808 | ambiguous | 0.4739 | ambiguous | -0.743 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.524271411 | None | None | N |
| D/C | 0.8873 | likely_pathogenic | 0.8695 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/E | 0.4591 | ambiguous | 0.4208 | ambiguous | -0.383 | Destabilizing | 1.0 | D | 0.382 | neutral | N | 0.490908198 | None | None | N |
| D/F | 0.9081 | likely_pathogenic | 0.8932 | pathogenic | -0.367 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/G | 0.4701 | ambiguous | 0.4602 | ambiguous | -1.004 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | N | 0.483396653 | None | None | N |
| D/H | 0.6793 | likely_pathogenic | 0.6476 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.496945459 | None | None | N |
| D/I | 0.8793 | likely_pathogenic | 0.8721 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/K | 0.8769 | likely_pathogenic | 0.8639 | pathogenic | 0.047 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/L | 0.7849 | likely_pathogenic | 0.7739 | pathogenic | -0.073 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/M | 0.9246 | likely_pathogenic | 0.9163 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| D/N | 0.3063 | likely_benign | 0.2886 | benign | -0.46 | Destabilizing | 1.0 | D | 0.652 | neutral | N | 0.512611622 | None | None | N |
| D/P | 0.9713 | likely_pathogenic | 0.965 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| D/Q | 0.7719 | likely_pathogenic | 0.7467 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/R | 0.8255 | likely_pathogenic | 0.816 | pathogenic | 0.273 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| D/S | 0.3419 | ambiguous | 0.3228 | benign | -0.61 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/T | 0.7098 | likely_pathogenic | 0.6847 | pathogenic | -0.39 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| D/V | 0.721 | likely_pathogenic | 0.7128 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.488271725 | None | None | N |
| D/W | 0.9697 | likely_pathogenic | 0.9675 | pathogenic | -0.077 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| D/Y | 0.6003 | likely_pathogenic | 0.591 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.502376735 | 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.