Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28706 | 86341;86342;86343 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| N2AB | 27065 | 81418;81419;81420 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| N2A | 26138 | 78637;78638;78639 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| N2B | 19641 | 59146;59147;59148 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| Novex-1 | 19766 | 59521;59522;59523 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| Novex-2 | 19833 | 59722;59723;59724 | chr2:178560016;178560015;178560014 | chr2:179424743;179424742;179424741 |
| 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/Q | rs199788826  |
-0.025 | 0.271 | N | 0.447 | 0.08 | None | gnomAD-2.1.1 | 7.46049E-04 | None | None | None | None | N | None | 0 | 1.1325E-04 | None | 0 | 1.03018E-04 | None | 3.56349E-03 | None | 2.95811E-03 | 9.46E-05 | 9.87028E-04 |
| R/Q | rs199788826 |
-0.025 | 0.271 | N | 0.447 | 0.08 | None | gnomAD-3.1.2 | 3.41826E-04 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 2.35671E-03 | 0 | 8.82E-05 | 3.93538E-03 | 0 |
| R/Q | rs199788826 |
-0.025 | 0.271 | N | 0.447 | 0.08 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| R/Q | rs199788826 |
-0.025 | 0.271 | N | 0.447 | 0.08 | None | gnomAD-4.0.0 | 3.61281E-04 | None | None | None | None | N | None | 3.99797E-05 | 6.668E-05 | None | 0 | 4.46588E-05 | None | 2.75146E-03 | 8.25083E-04 | 3.81422E-05 | 3.51347E-03 | 4.48172E-04 |
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 | 0.3569 | ambiguous | 0.3421 | ambiguous | -0.104 | Destabilizing | 0.035 | N | 0.379 | neutral | None | None | None | None | N |
| R/C | 0.1801 | likely_benign | 0.1825 | benign | -0.423 | Destabilizing | 0.935 | D | 0.346 | neutral | None | None | None | None | N |
| R/D | 0.6702 | likely_pathogenic | 0.635 | pathogenic | -0.33 | Destabilizing | 0.081 | N | 0.412 | neutral | None | None | None | None | N |
| R/E | 0.3879 | ambiguous | 0.358 | ambiguous | -0.305 | Destabilizing | 0.035 | N | 0.361 | neutral | None | None | None | None | N |
| R/F | 0.5177 | ambiguous | 0.5107 | ambiguous | -0.475 | Destabilizing | 0.791 | D | 0.349 | neutral | None | None | None | None | N |
| R/G | 0.2506 | likely_benign | 0.2458 | benign | -0.208 | Destabilizing | 0.144 | N | 0.394 | neutral | N | 0.469244847 | None | None | N |
| R/H | 0.1038 | likely_benign | 0.1009 | benign | -0.617 | Destabilizing | 0.555 | D | 0.463 | neutral | None | None | None | None | N |
| R/I | 0.2747 | likely_benign | 0.2578 | benign | 0.122 | Stabilizing | 0.555 | D | 0.38 | neutral | None | None | None | None | N |
| R/K | 0.0932 | likely_benign | 0.0937 | benign | -0.332 | Destabilizing | None | N | 0.162 | neutral | None | None | None | None | N |
| R/L | 0.2492 | likely_benign | 0.2369 | benign | 0.122 | Stabilizing | 0.251 | N | 0.426 | neutral | N | 0.469764922 | None | None | N |
| R/M | 0.2816 | likely_benign | 0.2618 | benign | -0.211 | Destabilizing | 0.791 | D | 0.416 | neutral | None | None | None | None | N |
| R/N | 0.5472 | ambiguous | 0.5159 | ambiguous | -0.264 | Destabilizing | 0.001 | N | 0.198 | neutral | None | None | None | None | N |
| R/P | 0.3884 | ambiguous | 0.3793 | ambiguous | 0.063 | Stabilizing | 0.705 | D | 0.389 | neutral | N | 0.438305865 | None | None | N |
| R/Q | 0.1062 | likely_benign | 0.1047 | benign | -0.303 | Destabilizing | 0.271 | N | 0.447 | neutral | N | 0.460662649 | None | None | N |
| R/S | 0.4652 | ambiguous | 0.4507 | ambiguous | -0.454 | Destabilizing | 0.035 | N | 0.383 | neutral | None | None | None | None | N |
| R/T | 0.2267 | likely_benign | 0.2092 | benign | -0.339 | Destabilizing | 0.149 | N | 0.435 | neutral | None | None | None | None | N |
| R/V | 0.3443 | ambiguous | 0.3336 | benign | 0.063 | Stabilizing | 0.149 | N | 0.393 | neutral | None | None | None | None | N |
| R/W | 0.1593 | likely_benign | 0.1638 | benign | -0.666 | Destabilizing | 0.935 | D | 0.428 | neutral | None | None | None | None | N |
| R/Y | 0.3676 | ambiguous | 0.356 | ambiguous | -0.28 | Destabilizing | 0.791 | D | 0.385 | neutral | None | None | 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.