Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5743 | 17452;17453;17454 | chr2:178731539;178731538;178731537 | chr2:179596266;179596265;179596264 |
| N2AB | 5426 | 16501;16502;16503 | chr2:178731539;178731538;178731537 | chr2:179596266;179596265;179596264 |
| N2A | 4499 | 13720;13721;13722 | chr2:178731539;178731538;178731537 | chr2:179596266;179596265;179596264 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs753892271  |
0.503 | None | N | 0.082 | 0.14 | 0.195762928549 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| R/L | rs753892271 |
0.503 | None | N | 0.082 | 0.14 | 0.195762928549 | gnomAD-4.0.0 | 6.84746E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16069E-05 | 0 |
| R/Q | rs753892271 |
0.075 | 0.004 | N | 0.221 | 0.055 | 0.0716867268079 | gnomAD-2.1.1 | 3.23072E-04 | None | None | None | None | I | None | 4.14E-05 | 2.35997E-03 | None | 0 | 5.17E-05 | None | 3.28E-05 | None | 4.02E-05 | 1.57E-05 | 1.41764E-04 |
| R/Q | rs753892271 |
0.075 | 0.004 | N | 0.221 | 0.055 | 0.0716867268079 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 1.96541E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs753892271 |
0.075 | 0.004 | N | 0.221 | 0.055 | 0.0716867268079 | gnomAD-4.0.0 | 7.31789E-05 | None | None | None | None | I | None | 8.01582E-05 | 1.51976E-03 | None | 3.38662E-05 | 4.47067E-05 | None | 1.56416E-05 | 0 | 9.32833E-06 | 2.19829E-05 | 6.41087E-05 |
| R/W | rs377193479 |
-0.315 | 0.99 | N | 0.225 | 0.173 | None | gnomAD-2.1.1 | 4.45E-05 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 9.84E-05 | None | 0 | 6.26E-05 | 0 |
| R/W | rs377193479 |
-0.315 | 0.99 | N | 0.225 | 0.173 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs377193479 |
-0.315 | 0.99 | N | 0.225 | 0.173 | None | gnomAD-4.0.0 | 3.03865E-05 | None | None | None | None | I | None | 1.33372E-05 | 1.66978E-05 | None | 0 | 0 | None | 0 | 0 | 3.39226E-05 | 6.59486E-05 | 1.602E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2933 | likely_benign | 0.2832 | benign | -0.14 | Destabilizing | 0.025 | N | 0.256 | neutral | None | None | None | None | I |
| R/C | 0.1774 | likely_benign | 0.1655 | benign | -0.247 | Destabilizing | 0.958 | D | 0.222 | neutral | None | None | None | None | I |
| R/D | 0.7227 | likely_pathogenic | 0.6722 | pathogenic | 0.032 | Stabilizing | 0.124 | N | 0.387 | neutral | None | None | None | None | I |
| R/E | 0.2971 | likely_benign | 0.2789 | benign | 0.111 | Stabilizing | 0.004 | N | 0.156 | neutral | None | None | None | None | I |
| R/F | 0.5102 | ambiguous | 0.4731 | ambiguous | -0.29 | Destabilizing | 0.497 | N | 0.319 | neutral | None | None | None | None | I |
| R/G | 0.2876 | likely_benign | 0.2756 | benign | -0.364 | Destabilizing | 0.351 | N | 0.332 | neutral | N | 0.488531536 | None | None | I |
| R/H | 0.1296 | likely_benign | 0.1242 | benign | -0.825 | Destabilizing | 0.497 | N | 0.265 | neutral | None | None | None | None | I |
| R/I | 0.1735 | likely_benign | 0.1666 | benign | 0.423 | Stabilizing | 0.001 | N | 0.176 | neutral | None | None | None | None | I |
| R/K | 0.1042 | likely_benign | 0.1039 | benign | -0.158 | Destabilizing | 0.055 | N | 0.256 | neutral | None | None | None | None | I |
| R/L | 0.1828 | likely_benign | 0.1749 | benign | 0.423 | Stabilizing | None | N | 0.082 | neutral | N | 0.367567982 | None | None | I |
| R/M | 0.2548 | likely_benign | 0.2574 | benign | 0.004 | Stabilizing | 0.497 | N | 0.275 | neutral | None | None | None | None | I |
| R/N | 0.5964 | likely_pathogenic | 0.5668 | pathogenic | 0.136 | Stabilizing | 0.22 | N | 0.293 | neutral | None | None | None | None | I |
| R/P | 0.4701 | ambiguous | 0.4461 | ambiguous | 0.257 | Stabilizing | 0.523 | D | 0.348 | neutral | N | 0.431638103 | None | None | I |
| R/Q | 0.0922 | likely_benign | 0.0928 | benign | 0.015 | Stabilizing | 0.004 | N | 0.221 | neutral | N | 0.4694257 | None | None | I |
| R/S | 0.4464 | ambiguous | 0.4266 | ambiguous | -0.332 | Destabilizing | 0.055 | N | 0.306 | neutral | None | None | None | None | I |
| R/T | 0.2242 | likely_benign | 0.2191 | benign | -0.104 | Destabilizing | 0.104 | N | 0.303 | neutral | None | None | None | None | I |
| R/V | 0.2447 | likely_benign | 0.2354 | benign | 0.257 | Stabilizing | 0.002 | N | 0.139 | neutral | None | None | None | None | I |
| R/W | 0.1716 | likely_benign | 0.1573 | benign | -0.256 | Destabilizing | 0.99 | D | 0.225 | neutral | N | 0.45934478 | None | None | I |
| R/Y | 0.3789 | ambiguous | 0.3316 | benign | 0.139 | Stabilizing | 0.667 | D | 0.319 | 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.