Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6329 | 19210;19211;19212 | chr2:178729053;178729052;178729051 | chr2:179593780;179593779;179593778 |
| N2AB | 6012 | 18259;18260;18261 | chr2:178729053;178729052;178729051 | chr2:179593780;179593779;179593778 |
| N2A | 5085 | 15478;15479;15480 | chr2:178729053;178729052;178729051 | chr2:179593780;179593779;179593778 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs748054208  |
0.202 | 0.993 | N | 0.623 | 0.305 | 0.213573922156 | gnomAD-2.1.1 | 8.13E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| D/N | rs748054208 |
0.202 | 0.993 | N | 0.623 | 0.305 | 0.213573922156 | gnomAD-4.0.0 | 4.78127E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58462E-06 | 0 | 0 |
| D/V | rs781304014 |
0.162 | 0.997 | N | 0.657 | 0.55 | 0.482792760554 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs781304014 |
0.162 | 0.997 | N | 0.657 | 0.55 | 0.482792760554 | gnomAD-4.0.0 | 4.7808E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.56328E-05 | None | 0 | 0 | 2.86128E-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 | 0.1946 | likely_benign | 0.2014 | benign | -0.207 | Destabilizing | 0.977 | D | 0.595 | neutral | N | 0.455478304 | None | None | I |
| D/C | 0.6089 | likely_pathogenic | 0.63 | pathogenic | 0.052 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| D/E | 0.1322 | likely_benign | 0.1435 | benign | -0.234 | Destabilizing | 0.117 | N | 0.271 | neutral | N | 0.441393737 | None | None | I |
| D/F | 0.5535 | ambiguous | 0.5672 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | I |
| D/G | 0.11 | likely_benign | 0.1134 | benign | -0.4 | Destabilizing | 0.977 | D | 0.629 | neutral | N | 0.37577646 | None | None | I |
| D/H | 0.2275 | likely_benign | 0.2396 | benign | -0.024 | Destabilizing | 0.999 | D | 0.629 | neutral | N | 0.465695748 | None | None | I |
| D/I | 0.3961 | ambiguous | 0.4247 | ambiguous | 0.251 | Stabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | I |
| D/K | 0.2572 | likely_benign | 0.2556 | benign | 0.29 | Stabilizing | 0.99 | D | 0.653 | neutral | None | None | None | None | I |
| D/L | 0.4095 | ambiguous | 0.418 | ambiguous | 0.251 | Stabilizing | 0.995 | D | 0.655 | neutral | None | None | None | None | I |
| D/M | 0.5632 | ambiguous | 0.588 | pathogenic | 0.355 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/N | 0.0778 | likely_benign | 0.0831 | benign | 0.074 | Stabilizing | 0.993 | D | 0.623 | neutral | N | 0.430542025 | None | None | I |
| D/P | 0.7758 | likely_pathogenic | 0.784 | pathogenic | 0.121 | Stabilizing | 0.998 | D | 0.648 | neutral | None | None | None | None | I |
| D/Q | 0.2524 | likely_benign | 0.26 | benign | 0.101 | Stabilizing | 0.99 | D | 0.659 | neutral | None | None | None | None | I |
| D/R | 0.2912 | likely_benign | 0.2862 | benign | 0.456 | Stabilizing | 0.995 | D | 0.615 | neutral | None | None | None | None | I |
| D/S | 0.1031 | likely_benign | 0.1099 | benign | -0.063 | Destabilizing | 0.983 | D | 0.573 | neutral | None | None | None | None | I |
| D/T | 0.2346 | likely_benign | 0.2469 | benign | 0.084 | Stabilizing | 0.995 | D | 0.651 | neutral | None | None | None | None | I |
| D/V | 0.2803 | likely_benign | 0.2965 | benign | 0.121 | Stabilizing | 0.997 | D | 0.657 | neutral | N | 0.492700773 | None | None | I |
| D/W | 0.8481 | likely_pathogenic | 0.8459 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| D/Y | 0.2366 | likely_benign | 0.2378 | benign | 0.051 | Stabilizing | 1.0 | D | 0.654 | neutral | N | 0.469570088 | 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.