Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21413 | 64462;64463;64464 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| N2AB | 19772 | 59539;59540;59541 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| N2A | 18845 | 56758;56759;56760 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| N2B | 12348 | 37267;37268;37269 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| Novex-1 | 12473 | 37642;37643;37644 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| Novex-2 | 12540 | 37843;37844;37845 | chr2:178586664;178586663;178586662 | chr2:179451391;179451390;179451389 |
| 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/G | rs375659466  |
0.041 | 0.008 | N | 0.389 | 0.21 | None | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| D/G | rs375659466 |
0.041 | 0.008 | N | 0.389 | 0.21 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| D/G | rs375659466 |
0.041 | 0.008 | N | 0.389 | 0.21 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| D/G | rs375659466 |
0.041 | 0.008 | N | 0.389 | 0.21 | None | gnomAD-4.0.0 | 4.4011E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.76557E-05 | 0 | 4.80384E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2382 | likely_benign | 0.2043 | benign | -0.202 | Destabilizing | 0.565 | D | 0.466 | neutral | N | 0.487691748 | None | None | N |
| D/C | 0.7401 | likely_pathogenic | 0.6745 | pathogenic | -0.193 | Destabilizing | 0.996 | D | 0.601 | neutral | None | None | None | None | N |
| D/E | 0.1324 | likely_benign | 0.1209 | benign | -0.231 | Destabilizing | 0.722 | D | 0.491 | neutral | N | 0.419562601 | None | None | N |
| D/F | 0.6764 | likely_pathogenic | 0.6105 | pathogenic | -0.147 | Destabilizing | 0.961 | D | 0.549 | neutral | None | None | None | None | N |
| D/G | 0.184 | likely_benign | 0.1615 | benign | -0.372 | Destabilizing | 0.008 | N | 0.389 | neutral | N | 0.41844788 | None | None | N |
| D/H | 0.3723 | ambiguous | 0.3174 | benign | 0.274 | Stabilizing | 0.041 | N | 0.523 | neutral | N | 0.462260069 | None | None | N |
| D/I | 0.5335 | ambiguous | 0.4484 | ambiguous | 0.195 | Stabilizing | 0.961 | D | 0.547 | neutral | None | None | None | None | N |
| D/K | 0.5387 | ambiguous | 0.4612 | ambiguous | 0.167 | Stabilizing | 0.923 | D | 0.474 | neutral | None | None | None | None | N |
| D/L | 0.4911 | ambiguous | 0.4146 | ambiguous | 0.195 | Stabilizing | 0.923 | D | 0.524 | neutral | None | None | None | None | N |
| D/M | 0.6851 | likely_pathogenic | 0.6136 | pathogenic | 0.095 | Stabilizing | 0.996 | D | 0.554 | neutral | None | None | None | None | N |
| D/N | 0.1331 | likely_benign | 0.1198 | benign | -0.041 | Destabilizing | 0.034 | N | 0.437 | neutral | N | 0.464238885 | None | None | N |
| D/P | 0.6751 | likely_pathogenic | 0.6111 | pathogenic | 0.083 | Stabilizing | 0.987 | D | 0.51 | neutral | None | None | None | None | N |
| D/Q | 0.4155 | ambiguous | 0.3545 | ambiguous | -0.014 | Destabilizing | 0.923 | D | 0.493 | neutral | None | None | None | None | N |
| D/R | 0.619 | likely_pathogenic | 0.5447 | ambiguous | 0.467 | Stabilizing | 0.923 | D | 0.519 | neutral | None | None | None | None | N |
| D/S | 0.1593 | likely_benign | 0.1391 | benign | -0.186 | Destabilizing | 0.775 | D | 0.477 | neutral | None | None | None | None | N |
| D/T | 0.3234 | likely_benign | 0.271 | benign | -0.054 | Destabilizing | 0.923 | D | 0.474 | neutral | None | None | None | None | N |
| D/V | 0.3385 | likely_benign | 0.2767 | benign | 0.083 | Stabilizing | 0.949 | D | 0.531 | neutral | N | 0.499215463 | None | None | N |
| D/W | 0.8919 | likely_pathogenic | 0.8514 | pathogenic | -0.045 | Destabilizing | 0.996 | D | 0.614 | neutral | None | None | None | None | N |
| D/Y | 0.3602 | ambiguous | 0.3007 | benign | 0.079 | Stabilizing | 0.901 | D | 0.546 | neutral | N | 0.511029968 | 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.