Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28308 | 85147;85148;85149 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| N2AB | 26667 | 80224;80225;80226 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| N2A | 25740 | 77443;77444;77445 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| N2B | 19243 | 57952;57953;57954 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| Novex-1 | 19368 | 58327;58328;58329 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| Novex-2 | 19435 | 58528;58529;58530 | chr2:178561210;178561209;178561208 | chr2:179425937;179425936;179425935 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | rs794729516  |
0.384 | 0.117 | N | 0.411 | 0.179 | 0.107399877778 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| Q/K | rs794729516 |
0.384 | 0.117 | N | 0.411 | 0.179 | 0.107399877778 | gnomAD-4.0.0 | 1.09496E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43912E-05 | 0 | 0 |
| Q/P | rs201674674 |
0.294 | None | N | 0.205 | 0.116 | None | gnomAD-2.1.1 | 2.03909E-04 | None | None | None | None | I | None | 4.13E-05 | 1.98222E-04 | None | 0 | 0 | None | 0 | None | 4.02E-05 | 3.60264E-04 | 2.81215E-04 |
| Q/P | rs201674674 |
0.294 | None | N | 0.205 | 0.116 | None | gnomAD-3.1.2 | 2.23446E-04 | None | None | None | None | I | None | 1.20645E-04 | 6.55E-05 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 3.82252E-04 | 0 | 4.78011E-04 |
| Q/P | rs201674674 |
0.294 | None | N | 0.205 | 0.116 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| Q/P | rs201674674 |
0.294 | None | N | 0.205 | 0.116 | None | gnomAD-4.0.0 | 2.60909E-04 | None | None | None | None | I | None | 6.66365E-05 | 2E-04 | None | 0 | 0 | None | 4.6991E-05 | 8.2481E-04 | 3.2124E-04 | 1.09801E-05 | 2.56115E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.1456 | likely_benign | 0.1559 | benign | -0.228 | Destabilizing | 0.035 | N | 0.399 | neutral | None | None | None | None | I |
| Q/C | 0.6061 | likely_pathogenic | 0.5995 | pathogenic | 0.114 | Stabilizing | 0.935 | D | 0.438 | neutral | None | None | None | None | I |
| Q/D | 0.3846 | ambiguous | 0.3809 | ambiguous | 0.055 | Stabilizing | 0.149 | N | 0.397 | neutral | None | None | None | None | I |
| Q/E | 0.0937 | likely_benign | 0.0964 | benign | 0.032 | Stabilizing | 0.052 | N | 0.387 | neutral | N | 0.45877435 | None | None | I |
| Q/F | 0.6785 | likely_pathogenic | 0.6905 | pathogenic | -0.398 | Destabilizing | 0.38 | N | 0.423 | neutral | None | None | None | None | I |
| Q/G | 0.2366 | likely_benign | 0.249 | benign | -0.42 | Destabilizing | 0.149 | N | 0.41 | neutral | None | None | None | None | I |
| Q/H | 0.2207 | likely_benign | 0.2113 | benign | -0.254 | Destabilizing | 0.741 | D | 0.401 | neutral | N | 0.474109162 | None | None | I |
| Q/I | 0.3199 | likely_benign | 0.3336 | benign | 0.193 | Stabilizing | 0.235 | N | 0.386 | neutral | None | None | None | None | I |
| Q/K | 0.1075 | likely_benign | 0.109 | benign | 0.048 | Stabilizing | 0.117 | N | 0.411 | neutral | N | 0.433203902 | None | None | I |
| Q/L | 0.1094 | likely_benign | 0.1217 | benign | 0.193 | Stabilizing | None | N | 0.251 | neutral | N | 0.408422888 | None | None | I |
| Q/M | 0.2782 | likely_benign | 0.2969 | benign | 0.366 | Stabilizing | 0.38 | N | 0.411 | neutral | None | None | None | None | I |
| Q/N | 0.2536 | likely_benign | 0.2539 | benign | -0.279 | Destabilizing | 0.555 | D | 0.39 | neutral | None | None | None | None | I |
| Q/P | 0.067 | likely_benign | 0.0788 | benign | 0.081 | Stabilizing | None | N | 0.205 | neutral | N | 0.436974926 | None | None | I |
| Q/R | 0.1157 | likely_benign | 0.1173 | benign | 0.215 | Stabilizing | 0.211 | N | 0.42 | neutral | N | 0.445402408 | None | None | I |
| Q/S | 0.1555 | likely_benign | 0.1707 | benign | -0.286 | Destabilizing | 0.149 | N | 0.376 | neutral | None | None | None | None | I |
| Q/T | 0.1255 | likely_benign | 0.1415 | benign | -0.15 | Destabilizing | 0.149 | N | 0.408 | neutral | None | None | None | None | I |
| Q/V | 0.1946 | likely_benign | 0.2138 | benign | 0.081 | Stabilizing | 0.081 | N | 0.392 | neutral | None | None | None | None | I |
| Q/W | 0.5875 | likely_pathogenic | 0.5738 | pathogenic | -0.368 | Destabilizing | 0.935 | D | 0.465 | neutral | None | None | None | None | I |
| Q/Y | 0.486 | ambiguous | 0.4728 | ambiguous | -0.117 | Destabilizing | 0.555 | D | 0.419 | 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.