Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33641 | 101146;101147;101148 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| N2AB | 32000 | 96223;96224;96225 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| N2A | 31073 | 93442;93443;93444 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| N2B | 24576 | 73951;73952;73953 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| Novex-1 | 24701 | 74326;74327;74328 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| Novex-2 | 24768 | 74527;74528;74529 | chr2:178535694;178535693;178535692 | chr2:179400421;179400420;179400419 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Q | rs1691127745  |
None | 0.042 | N | 0.131 | 0.132 | 0.107399877778 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| H/R | rs759457802 |
-0.984 | 0.608 | N | 0.244 | 0.202 | 0.0954503805726 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.66908E-04 | None | 0 | None | 0 | 0 | 0 |
| H/R | rs759457802 |
-0.984 | 0.608 | N | 0.244 | 0.202 | 0.0954503805726 | gnomAD-4.0.0 | 3.18251E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.54508E-05 | None | 0 | 0 | 0 | 0 | 0 |
| H/Y | rs1357251504 |
0.759 | 0.024 | N | 0.109 | 0.145 | 0.167679373172 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/Y | rs1357251504 |
0.759 | 0.024 | N | 0.109 | 0.145 | 0.167679373172 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | N | None | 0 | 2.28634E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.4353 | ambiguous | 0.3383 | benign | -1.015 | Destabilizing | 0.81 | D | 0.285 | neutral | None | None | None | None | N |
| H/C | 0.3015 | likely_benign | 0.2455 | benign | -0.08 | Destabilizing | 0.996 | D | 0.373 | neutral | None | None | None | None | N |
| H/D | 0.3926 | ambiguous | 0.2885 | benign | -0.762 | Destabilizing | 0.701 | D | 0.353 | neutral | N | 0.458035271 | None | None | N |
| H/E | 0.4738 | ambiguous | 0.3591 | ambiguous | -0.617 | Destabilizing | 0.47 | N | 0.258 | neutral | None | None | None | None | N |
| H/F | 0.4417 | ambiguous | 0.3489 | ambiguous | 0.518 | Stabilizing | 0.742 | D | 0.346 | neutral | None | None | None | None | N |
| H/G | 0.5279 | ambiguous | 0.4159 | ambiguous | -1.432 | Destabilizing | 0.912 | D | 0.327 | neutral | None | None | None | None | N |
| H/I | 0.4239 | ambiguous | 0.3386 | benign | 0.172 | Stabilizing | 0.967 | D | 0.445 | neutral | None | None | None | None | N |
| H/K | 0.3904 | ambiguous | 0.2612 | benign | -0.432 | Destabilizing | 0.023 | N | 0.167 | neutral | None | None | None | None | N |
| H/L | 0.2105 | likely_benign | 0.1753 | benign | 0.172 | Stabilizing | 0.561 | D | 0.381 | neutral | N | 0.506597222 | None | None | N |
| H/M | 0.5866 | likely_pathogenic | 0.5018 | ambiguous | -0.01 | Destabilizing | 0.989 | D | 0.367 | neutral | None | None | None | None | N |
| H/N | 0.1263 | likely_benign | 0.1009 | benign | -0.762 | Destabilizing | 0.701 | D | 0.274 | neutral | N | 0.453648171 | None | None | N |
| H/P | 0.3566 | ambiguous | 0.2905 | benign | -0.206 | Destabilizing | 0.943 | D | 0.412 | neutral | N | 0.506943938 | None | None | N |
| H/Q | 0.224 | likely_benign | 0.1758 | benign | -0.461 | Destabilizing | 0.042 | N | 0.131 | neutral | N | 0.477410465 | None | None | N |
| H/R | 0.1774 | likely_benign | 0.1273 | benign | -0.928 | Destabilizing | 0.608 | D | 0.244 | neutral | N | 0.374565738 | None | None | N |
| H/S | 0.3242 | likely_benign | 0.2478 | benign | -0.829 | Destabilizing | 0.81 | D | 0.32 | neutral | None | None | None | None | N |
| H/T | 0.376 | ambiguous | 0.2836 | benign | -0.563 | Destabilizing | 0.756 | D | 0.355 | neutral | None | None | None | None | N |
| H/V | 0.3895 | ambiguous | 0.322 | benign | -0.206 | Destabilizing | 0.811 | D | 0.411 | neutral | None | None | None | None | N |
| H/W | 0.5855 | likely_pathogenic | 0.504 | ambiguous | 0.958 | Stabilizing | 0.999 | D | 0.352 | neutral | None | None | None | None | N |
| H/Y | 0.1491 | likely_benign | 0.1131 | benign | 0.924 | Stabilizing | 0.024 | N | 0.109 | neutral | N | 0.469772417 | 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.