Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28494 | 85705;85706;85707 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| N2AB | 26853 | 80782;80783;80784 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| N2A | 25926 | 78001;78002;78003 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| N2B | 19429 | 58510;58511;58512 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| Novex-1 | 19554 | 58885;58886;58887 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| Novex-2 | 19621 | 59086;59087;59088 | chr2:178560652;178560651;178560650 | chr2:179425379;179425378;179425377 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs749807293  |
-0.376 | 0.892 | N | 0.313 | 0.189 | 0.229924730088 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/G | rs749807293 |
-0.376 | 0.892 | N | 0.313 | 0.189 | 0.229924730088 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| S/G | rs749807293 |
-0.376 | 0.892 | N | 0.313 | 0.189 | 0.229924730088 | gnomAD-4.0.0 | 3.84381E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.14238E-05 | 0 | 0 | 1.34002E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1501 | likely_benign | 0.1405 | benign | -0.157 | Destabilizing | 0.818 | D | 0.361 | neutral | None | None | None | None | I |
| S/C | 0.2274 | likely_benign | 0.253 | benign | -0.237 | Destabilizing | 0.999 | D | 0.43 | neutral | N | 0.505072534 | None | None | I |
| S/D | 0.6193 | likely_pathogenic | 0.6411 | pathogenic | -0.087 | Destabilizing | 0.957 | D | 0.3 | neutral | None | None | None | None | I |
| S/E | 0.7648 | likely_pathogenic | 0.7702 | pathogenic | -0.191 | Destabilizing | 0.916 | D | 0.324 | neutral | None | None | None | None | I |
| S/F | 0.4797 | ambiguous | 0.4945 | ambiguous | -0.789 | Destabilizing | 0.996 | D | 0.483 | neutral | None | None | None | None | I |
| S/G | 0.1482 | likely_benign | 0.1495 | benign | -0.24 | Destabilizing | 0.892 | D | 0.313 | neutral | N | 0.488809256 | None | None | I |
| S/H | 0.5487 | ambiguous | 0.5782 | pathogenic | -0.605 | Destabilizing | 0.997 | D | 0.384 | neutral | None | None | None | None | I |
| S/I | 0.4431 | ambiguous | 0.4422 | ambiguous | -0.07 | Destabilizing | 0.983 | D | 0.484 | neutral | N | 0.504819044 | None | None | I |
| S/K | 0.8105 | likely_pathogenic | 0.8208 | pathogenic | -0.475 | Destabilizing | 0.845 | D | 0.32 | neutral | None | None | None | None | I |
| S/L | 0.2021 | likely_benign | 0.1993 | benign | -0.07 | Destabilizing | 0.916 | D | 0.377 | neutral | None | None | None | None | I |
| S/M | 0.4408 | ambiguous | 0.4264 | ambiguous | -0.002 | Destabilizing | 0.999 | D | 0.389 | neutral | None | None | None | None | I |
| S/N | 0.2792 | likely_benign | 0.2891 | benign | -0.114 | Destabilizing | 0.892 | D | 0.315 | neutral | N | 0.509992604 | None | None | I |
| S/P | 0.5428 | ambiguous | 0.5715 | pathogenic | -0.072 | Destabilizing | 0.996 | D | 0.399 | neutral | None | None | None | None | I |
| S/Q | 0.7184 | likely_pathogenic | 0.7171 | pathogenic | -0.376 | Destabilizing | 0.975 | D | 0.348 | neutral | None | None | None | None | I |
| S/R | 0.7234 | likely_pathogenic | 0.7366 | pathogenic | -0.177 | Destabilizing | 0.056 | N | 0.283 | neutral | N | 0.473330568 | None | None | I |
| S/T | 0.1538 | likely_benign | 0.1453 | benign | -0.213 | Destabilizing | 0.892 | D | 0.336 | neutral | N | 0.470292374 | None | None | I |
| S/V | 0.4192 | ambiguous | 0.4076 | ambiguous | -0.072 | Destabilizing | 0.987 | D | 0.46 | neutral | None | None | None | None | I |
| S/W | 0.5535 | ambiguous | 0.5834 | pathogenic | -0.859 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| S/Y | 0.3876 | ambiguous | 0.4121 | ambiguous | -0.561 | Destabilizing | 0.996 | D | 0.486 | 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.