Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29703 | 89332;89333;89334 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| N2AB | 28062 | 84409;84410;84411 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| N2A | 27135 | 81628;81629;81630 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| N2B | 20638 | 62137;62138;62139 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| Novex-1 | 20763 | 62512;62513;62514 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| Novex-2 | 20830 | 62713;62714;62715 | chr2:178554004;178554003;178554002 | chr2:179418731;179418730;179418729 |
| 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 | rs1368949216  |
-0.782 | None | N | 0.13 | 0.143 | 0.0762999501168 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/V | rs1700334613 |
None | 0.117 | N | 0.597 | 0.242 | 0.46512379133 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| D/V | rs1700334613 |
None | 0.117 | N | 0.597 | 0.242 | 0.46512379133 | gnomAD-4.0.0 | 3.84485E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.73754E-05 | 0 | 0 | 0 | 0 |
| D/Y | rs1429421793 |
-0.573 | 0.741 | N | 0.672 | 0.287 | 0.520803792171 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/Y | rs1429421793 |
-0.573 | 0.741 | N | 0.672 | 0.287 | 0.520803792171 | gnomAD-4.0.0 | 1.75151E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.57607E-04 | 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 | 0.1698 | likely_benign | 0.1513 | benign | -0.904 | Destabilizing | 0.027 | N | 0.442 | neutral | N | 0.453699391 | None | None | N |
| D/C | 0.5036 | ambiguous | 0.4525 | ambiguous | -0.515 | Destabilizing | 0.935 | D | 0.667 | neutral | None | None | None | None | N |
| D/E | 0.11 | likely_benign | 0.1036 | benign | -0.733 | Destabilizing | None | N | 0.13 | neutral | N | 0.33229312 | None | None | N |
| D/F | 0.4153 | ambiguous | 0.4031 | ambiguous | -0.535 | Destabilizing | 0.791 | D | 0.672 | neutral | None | None | None | None | N |
| D/G | 0.3132 | likely_benign | 0.2644 | benign | -1.316 | Destabilizing | 0.052 | N | 0.449 | neutral | N | 0.479808557 | None | None | N |
| D/H | 0.2746 | likely_benign | 0.2381 | benign | -0.89 | Destabilizing | 0.484 | N | 0.557 | neutral | N | 0.50934203 | None | None | N |
| D/I | 0.217 | likely_benign | 0.2012 | benign | 0.223 | Stabilizing | 0.555 | D | 0.645 | neutral | None | None | None | None | N |
| D/K | 0.4621 | ambiguous | 0.4224 | ambiguous | -1.137 | Destabilizing | 0.035 | N | 0.445 | neutral | None | None | None | None | N |
| D/L | 0.2474 | likely_benign | 0.2444 | benign | 0.223 | Stabilizing | 0.149 | N | 0.593 | neutral | None | None | None | None | N |
| D/M | 0.4175 | ambiguous | 0.4116 | ambiguous | 0.909 | Stabilizing | 0.935 | D | 0.649 | neutral | None | None | None | None | N |
| D/N | 0.1029 | likely_benign | 0.1001 | benign | -1.434 | Destabilizing | 0.117 | N | 0.456 | neutral | N | 0.472053079 | None | None | N |
| D/P | 0.7141 | likely_pathogenic | 0.7287 | pathogenic | -0.129 | Destabilizing | 0.262 | N | 0.54 | neutral | None | None | None | None | N |
| D/Q | 0.2896 | likely_benign | 0.2606 | benign | -1.184 | Destabilizing | 0.081 | N | 0.435 | neutral | None | None | None | None | N |
| D/R | 0.5213 | ambiguous | 0.4641 | ambiguous | -1.019 | Destabilizing | 0.081 | N | 0.612 | neutral | None | None | None | None | N |
| D/S | 0.1193 | likely_benign | 0.1131 | benign | -1.95 | Destabilizing | 0.007 | N | 0.153 | neutral | None | None | None | None | N |
| D/T | 0.1902 | likely_benign | 0.1764 | benign | -1.594 | Destabilizing | 0.081 | N | 0.445 | neutral | None | None | None | None | N |
| D/V | 0.1498 | likely_benign | 0.1306 | benign | -0.129 | Destabilizing | 0.117 | N | 0.597 | neutral | N | 0.454392825 | None | None | N |
| D/W | 0.8373 | likely_pathogenic | 0.815 | pathogenic | -0.504 | Destabilizing | 0.935 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/Y | 0.1817 | likely_benign | 0.1604 | benign | -0.349 | Destabilizing | 0.741 | D | 0.672 | neutral | N | 0.503936211 | 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.