Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29876 | 89851;89852;89853 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| N2AB | 28235 | 84928;84929;84930 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| N2A | 27308 | 82147;82148;82149 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| N2B | 20811 | 62656;62657;62658 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| Novex-1 | 20936 | 63031;63032;63033 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| Novex-2 | 21003 | 63232;63233;63234 | chr2:178553274;178553273;178553272 | chr2:179418001;179418000;179417999 |
| 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 | rs397517743  |
-0.017 | None | N | 0.127 | 0.101 | 0.0716867268079 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.28811E-04 | 7.81E-06 | 0 |
| D/E | rs397517743 |
-0.017 | None | N | 0.127 | 0.101 | 0.0716867268079 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs397517743 |
-0.017 | None | N | 0.127 | 0.101 | 0.0716867268079 | gnomAD-4.0.0 | 1.67543E-05 | None | None | None | None | N | None | 0 | 1.66661E-05 | None | 0 | 0 | None | 4.85814E-05 | 0 | 1.77995E-05 | 0 | 3.20277E-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 | 0.1624 | likely_benign | 0.1459 | benign | 0.003 | Stabilizing | 0.019 | N | 0.363 | neutral | N | 0.50254377 | None | None | N |
| D/C | 0.5909 | likely_pathogenic | 0.6063 | pathogenic | 0.035 | Stabilizing | 0.958 | D | 0.399 | neutral | None | None | None | None | N |
| D/E | 0.1278 | likely_benign | 0.1226 | benign | -0.192 | Destabilizing | None | N | 0.127 | neutral | N | 0.44557298 | None | None | N |
| D/F | 0.6078 | likely_pathogenic | 0.573 | pathogenic | -0.043 | Destabilizing | 0.859 | D | 0.425 | neutral | None | None | None | None | N |
| D/G | 0.0789 | likely_benign | 0.0811 | benign | -0.148 | Destabilizing | None | N | 0.152 | neutral | N | 0.467350974 | None | None | N |
| D/H | 0.3391 | likely_benign | 0.3443 | ambiguous | 0.336 | Stabilizing | 0.602 | D | 0.375 | neutral | N | 0.49989693 | None | None | N |
| D/I | 0.4499 | ambiguous | 0.4118 | ambiguous | 0.337 | Stabilizing | 0.667 | D | 0.453 | neutral | None | None | None | None | N |
| D/K | 0.3467 | ambiguous | 0.3704 | ambiguous | 0.476 | Stabilizing | 0.055 | N | 0.381 | neutral | None | None | None | None | N |
| D/L | 0.3818 | ambiguous | 0.3605 | ambiguous | 0.337 | Stabilizing | 0.22 | N | 0.488 | neutral | None | None | None | None | N |
| D/M | 0.5537 | ambiguous | 0.5268 | ambiguous | 0.246 | Stabilizing | 0.958 | D | 0.4 | neutral | None | None | None | None | N |
| D/N | 0.0985 | likely_benign | 0.0987 | benign | 0.252 | Stabilizing | 0.003 | N | 0.121 | neutral | N | 0.452186734 | None | None | N |
| D/P | 0.7424 | likely_pathogenic | 0.7208 | pathogenic | 0.247 | Stabilizing | 0.364 | N | 0.448 | neutral | None | None | None | None | N |
| D/Q | 0.2935 | likely_benign | 0.3052 | benign | 0.267 | Stabilizing | 0.124 | N | 0.243 | neutral | None | None | None | None | N |
| D/R | 0.3912 | ambiguous | 0.4106 | ambiguous | 0.656 | Stabilizing | 0.22 | N | 0.484 | neutral | None | None | None | None | N |
| D/S | 0.1463 | likely_benign | 0.1401 | benign | 0.146 | Stabilizing | 0.005 | N | 0.12 | neutral | None | None | None | None | N |
| D/T | 0.3203 | likely_benign | 0.2962 | benign | 0.264 | Stabilizing | 0.055 | N | 0.385 | neutral | None | None | None | None | N |
| D/V | 0.2765 | likely_benign | 0.2417 | benign | 0.247 | Stabilizing | 0.175 | N | 0.491 | neutral | N | 0.461308564 | None | None | N |
| D/W | 0.8263 | likely_pathogenic | 0.8164 | pathogenic | 0.015 | Stabilizing | 0.958 | D | 0.419 | neutral | None | None | None | None | N |
| D/Y | 0.2469 | likely_benign | 0.2355 | benign | 0.186 | Stabilizing | 0.822 | D | 0.425 | neutral | N | 0.485008679 | 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.