Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18522 | 55789;55790;55791 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| N2AB | 16881 | 50866;50867;50868 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| N2A | 15954 | 48085;48086;48087 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| N2B | 9457 | 28594;28595;28596 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| Novex-1 | 9582 | 28969;28970;28971 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| Novex-2 | 9649 | 29170;29171;29172 | chr2:178601433;178601432;178601431 | chr2:179466160;179466159;179466158 |
| 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 | None | None | 0.012 | N | 0.289 | 0.063 | 0.168933306366 | 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 |
| D/V | rs1211576470  |
0.373 | 0.669 | N | 0.307 | 0.261 | 0.409533910539 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs1211576470 |
0.373 | 0.669 | N | 0.307 | 0.261 | 0.409533910539 | gnomAD-4.0.0 | 1.59308E-06 | None | None | None | None | N | None | 0 | 2.28896E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1942 | likely_benign | 0.2573 | benign | 0.011 | Stabilizing | 0.625 | D | 0.284 | neutral | N | 0.436020495 | None | None | N |
| D/C | 0.6578 | likely_pathogenic | 0.7498 | pathogenic | 0.019 | Stabilizing | 0.998 | D | 0.261 | neutral | None | None | None | None | N |
| D/E | 0.1392 | likely_benign | 0.166 | benign | -0.296 | Destabilizing | 0.012 | N | 0.289 | neutral | N | 0.432748116 | None | None | N |
| D/F | 0.6453 | likely_pathogenic | 0.7565 | pathogenic | -0.107 | Destabilizing | 0.974 | D | 0.272 | neutral | None | None | None | None | N |
| D/G | 0.201 | likely_benign | 0.2718 | benign | -0.091 | Destabilizing | 0.801 | D | 0.294 | neutral | N | 0.389725271 | None | None | N |
| D/H | 0.3291 | likely_benign | 0.4336 | ambiguous | 0.414 | Stabilizing | 0.966 | D | 0.269 | neutral | N | 0.46249502 | None | None | N |
| D/I | 0.4716 | ambiguous | 0.602 | pathogenic | 0.211 | Stabilizing | 0.142 | N | 0.303 | neutral | None | None | None | None | N |
| D/K | 0.4501 | ambiguous | 0.5793 | pathogenic | 0.563 | Stabilizing | 0.728 | D | 0.291 | neutral | None | None | None | None | N |
| D/L | 0.4332 | ambiguous | 0.5288 | ambiguous | 0.211 | Stabilizing | 0.728 | D | 0.304 | neutral | None | None | None | None | N |
| D/M | 0.631 | likely_pathogenic | 0.7399 | pathogenic | 0.116 | Stabilizing | 0.993 | D | 0.249 | neutral | None | None | None | None | N |
| D/N | 0.1234 | likely_benign | 0.155 | benign | 0.312 | Stabilizing | 0.051 | N | 0.21 | neutral | N | 0.430033098 | None | None | N |
| D/P | 0.7309 | likely_pathogenic | 0.8439 | pathogenic | 0.163 | Stabilizing | 0.974 | D | 0.291 | neutral | None | None | None | None | N |
| D/Q | 0.3502 | ambiguous | 0.4478 | ambiguous | 0.31 | Stabilizing | 0.904 | D | 0.235 | neutral | None | None | None | None | N |
| D/R | 0.475 | ambiguous | 0.6116 | pathogenic | 0.704 | Stabilizing | 0.949 | D | 0.301 | neutral | None | None | None | None | N |
| D/S | 0.1339 | likely_benign | 0.1746 | benign | 0.24 | Stabilizing | 0.525 | D | 0.274 | neutral | None | None | None | None | N |
| D/T | 0.2226 | likely_benign | 0.2871 | benign | 0.328 | Stabilizing | 0.029 | N | 0.209 | neutral | None | None | None | None | N |
| D/V | 0.3137 | likely_benign | 0.4124 | ambiguous | 0.163 | Stabilizing | 0.669 | D | 0.307 | neutral | N | 0.486121241 | None | None | N |
| D/W | 0.8725 | likely_pathogenic | 0.9211 | pathogenic | -0.072 | Destabilizing | 0.998 | D | 0.381 | neutral | None | None | None | None | N |
| D/Y | 0.3216 | likely_benign | 0.4051 | ambiguous | 0.117 | Stabilizing | 0.989 | D | 0.269 | neutral | N | 0.508459383 | 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.