Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20973 | 63142;63143;63144 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| N2AB | 19332 | 58219;58220;58221 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| N2A | 18405 | 55438;55439;55440 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| N2B | 11908 | 35947;35948;35949 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| Novex-1 | 12033 | 36322;36323;36324 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| Novex-2 | 12100 | 36523;36524;36525 | chr2:178588808;178588807;178588806 | chr2:179453535;179453534;179453533 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs374657513  |
-0.355 | 0.999 | N | 0.597 | 0.26 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/A | rs374657513 |
-0.355 | 0.999 | N | 0.597 | 0.26 | None | gnomAD-4.0.0 | 3.18432E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77901E-05 | None | 0 | 0 | 2.85956E-06 | 0 | 0 |
| T/P | rs374657513 |
-0.226 | 1.0 | D | 0.841 | 0.33 | 0.416707687347 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 0 | 0 |
| T/P | rs374657513 |
-0.226 | 1.0 | D | 0.841 | 0.33 | 0.416707687347 | gnomAD-4.0.0 | 1.59216E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88317E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2157 | likely_benign | 0.1544 | benign | -0.483 | Destabilizing | 0.999 | D | 0.597 | neutral | N | 0.518270945 | None | None | N |
| T/C | 0.6392 | likely_pathogenic | 0.5365 | ambiguous | -0.355 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| T/D | 0.7871 | likely_pathogenic | 0.6473 | pathogenic | 0.116 | Stabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| T/E | 0.676 | likely_pathogenic | 0.5126 | ambiguous | 0.079 | Stabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| T/F | 0.5427 | ambiguous | 0.4025 | ambiguous | -0.693 | Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| T/G | 0.4195 | ambiguous | 0.304 | benign | -0.688 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| T/H | 0.6183 | likely_pathogenic | 0.4667 | ambiguous | -0.941 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| T/I | 0.4412 | ambiguous | 0.4171 | ambiguous | -0.047 | Destabilizing | 1.0 | D | 0.832 | deleterious | N | 0.512267692 | None | None | N |
| T/K | 0.587 | likely_pathogenic | 0.4459 | ambiguous | -0.577 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| T/L | 0.2068 | likely_benign | 0.15 | benign | -0.047 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | None | None | None | None | N |
| T/M | 0.1526 | likely_benign | 0.1225 | benign | 0.07 | Stabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| T/N | 0.3284 | likely_benign | 0.2239 | benign | -0.405 | Destabilizing | 1.0 | D | 0.744 | deleterious | N | 0.491691993 | None | None | N |
| T/P | 0.7638 | likely_pathogenic | 0.6007 | pathogenic | -0.16 | Destabilizing | 1.0 | D | 0.841 | deleterious | D | 0.525871708 | None | None | N |
| T/Q | 0.4901 | ambiguous | 0.3769 | ambiguous | -0.579 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| T/R | 0.5434 | ambiguous | 0.3972 | ambiguous | -0.319 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| T/S | 0.1841 | likely_benign | 0.136 | benign | -0.653 | Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.449253577 | None | None | N |
| T/V | 0.2968 | likely_benign | 0.227 | benign | -0.16 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| T/W | 0.8375 | likely_pathogenic | 0.7366 | pathogenic | -0.672 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| T/Y | 0.6535 | likely_pathogenic | 0.4787 | ambiguous | -0.423 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | 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.