Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1846 | 5761;5762;5763 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| N2AB | 1846 | 5761;5762;5763 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| N2A | 1846 | 5761;5762;5763 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| N2B | 1800 | 5623;5624;5625 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| Novex-1 | 1800 | 5623;5624;5625 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| Novex-2 | 1800 | 5623;5624;5625 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
| Novex-3 | 1846 | 5761;5762;5763 | chr2:178776328;178776327;178776326 | chr2:179641055;179641054;179641053 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs746592442  |
-0.313 | 0.427 | N | 0.442 | 0.12 | 0.430351802785 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | I | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/C | rs746592442 |
-0.313 | 0.427 | N | 0.442 | 0.12 | 0.430351802785 | gnomAD-4.0.0 | 1.59093E-06 | None | None | None | None | I | None | 5.65291E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.2317 | likely_benign | 0.2694 | benign | -1.736 | Destabilizing | 0.002 | N | 0.347 | neutral | None | None | None | None | I |
| Y/C | 0.1202 | likely_benign | 0.1313 | benign | -0.581 | Destabilizing | 0.427 | N | 0.442 | neutral | N | 0.499307592 | None | None | I |
| Y/D | 0.4182 | ambiguous | 0.4687 | ambiguous | -0.795 | Destabilizing | 0.065 | N | 0.549 | neutral | N | 0.477023038 | None | None | I |
| Y/E | 0.464 | ambiguous | 0.532 | ambiguous | -0.745 | Destabilizing | 0.018 | N | 0.422 | neutral | None | None | None | None | I |
| Y/F | 0.0358 | likely_benign | 0.0355 | benign | -0.859 | Destabilizing | None | N | 0.091 | neutral | N | 0.459980124 | None | None | I |
| Y/G | 0.417 | ambiguous | 0.4694 | ambiguous | -2.007 | Highly Destabilizing | 0.037 | N | 0.397 | neutral | None | None | None | None | I |
| Y/H | 0.1587 | likely_benign | 0.1874 | benign | -0.668 | Destabilizing | 0.196 | N | 0.399 | neutral | N | 0.416448614 | None | None | I |
| Y/I | 0.1128 | likely_benign | 0.1148 | benign | -0.939 | Destabilizing | 0.004 | N | 0.291 | neutral | None | None | None | None | I |
| Y/K | 0.3963 | ambiguous | 0.4864 | ambiguous | -0.915 | Destabilizing | 0.009 | N | 0.365 | neutral | None | None | None | None | I |
| Y/L | 0.265 | likely_benign | 0.277 | benign | -0.939 | Destabilizing | None | N | 0.165 | neutral | None | None | None | None | I |
| Y/M | 0.2525 | likely_benign | 0.2807 | benign | -0.696 | Destabilizing | 0.044 | N | 0.487 | neutral | None | None | None | None | I |
| Y/N | 0.191 | likely_benign | 0.2107 | benign | -1.262 | Destabilizing | 0.065 | N | 0.532 | neutral | N | 0.417729981 | None | None | I |
| Y/P | 0.5226 | ambiguous | 0.6171 | pathogenic | -1.197 | Destabilizing | 0.22 | N | 0.574 | neutral | None | None | None | None | I |
| Y/Q | 0.2851 | likely_benign | 0.3483 | ambiguous | -1.186 | Destabilizing | 0.085 | N | 0.469 | neutral | None | None | None | None | I |
| Y/R | 0.3022 | likely_benign | 0.371 | ambiguous | -0.569 | Destabilizing | None | N | 0.252 | neutral | None | None | None | None | I |
| Y/S | 0.1406 | likely_benign | 0.1577 | benign | -1.601 | Destabilizing | 0.028 | N | 0.361 | neutral | N | 0.419833638 | None | None | I |
| Y/T | 0.2069 | likely_benign | 0.2343 | benign | -1.454 | Destabilizing | 0.018 | N | 0.359 | neutral | None | None | None | None | I |
| Y/V | 0.1015 | likely_benign | 0.1067 | benign | -1.197 | Destabilizing | None | N | 0.172 | neutral | None | None | None | None | I |
| Y/W | 0.3068 | likely_benign | 0.3324 | benign | -0.689 | Destabilizing | 0.245 | N | 0.383 | 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.