Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20858 | 62797;62798;62799 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| N2AB | 19217 | 57874;57875;57876 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| N2A | 18290 | 55093;55094;55095 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| N2B | 11793 | 35602;35603;35604 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| Novex-1 | 11918 | 35977;35978;35979 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| Novex-2 | 11985 | 36178;36179;36180 | chr2:178589153;178589152;178589151 | chr2:179453880;179453879;179453878 |
| 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 | rs200689750  |
-0.79 | 0.454 | N | 0.477 | 0.218 | None | gnomAD-2.1.1 | 3.82624E-04 | None | None | None | None | N | None | 8.27E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 1.20385E-04 | 7.58951E-04 | 5.6243E-04 |
| T/A | rs200689750 |
-0.79 | 0.454 | N | 0.477 | 0.218 | None | gnomAD-3.1.2 | 2.76145E-04 | None | None | None | None | N | None | 2.41E-05 | 1.3101E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.73681E-04 | 0 | 0 |
| T/A | rs200689750 |
-0.79 | 0.454 | N | 0.477 | 0.218 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs200689750 |
-0.79 | 0.454 | N | 0.477 | 0.218 | None | gnomAD-4.0.0 | 5.65294E-04 | None | None | None | None | N | None | 5.33049E-05 | 8.33556E-05 | None | 0 | 0 | None | 1.87911E-04 | 0 | 7.39219E-04 | 0 | 3.04204E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0881 | likely_benign | 0.0853 | benign | -0.732 | Destabilizing | 0.454 | N | 0.477 | neutral | N | 0.521399756 | None | None | N |
| T/C | 0.4623 | ambiguous | 0.4944 | ambiguous | -0.506 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| T/D | 0.4772 | ambiguous | 0.483 | ambiguous | 0.223 | Stabilizing | 0.728 | D | 0.559 | neutral | None | None | None | None | N |
| T/E | 0.3877 | ambiguous | 0.3961 | ambiguous | 0.296 | Stabilizing | 0.842 | D | 0.541 | neutral | None | None | None | None | N |
| T/F | 0.2981 | likely_benign | 0.2777 | benign | -0.684 | Destabilizing | 0.991 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/G | 0.3338 | likely_benign | 0.334 | benign | -1.046 | Destabilizing | 0.525 | D | 0.585 | neutral | None | None | None | None | N |
| T/H | 0.2966 | likely_benign | 0.2974 | benign | -1.185 | Destabilizing | 0.974 | D | 0.704 | prob.neutral | None | None | None | None | N |
| T/I | 0.1729 | likely_benign | 0.1627 | benign | 0.028 | Stabilizing | 0.966 | D | 0.65 | neutral | N | 0.503507428 | None | None | N |
| T/K | 0.2848 | likely_benign | 0.2994 | benign | -0.356 | Destabilizing | 0.842 | D | 0.537 | neutral | None | None | None | None | N |
| T/L | 0.1078 | likely_benign | 0.1044 | benign | 0.028 | Stabilizing | 0.842 | D | 0.542 | neutral | None | None | None | None | N |
| T/M | 0.092 | likely_benign | 0.0932 | benign | -0.014 | Destabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | N |
| T/N | 0.1368 | likely_benign | 0.1352 | benign | -0.546 | Destabilizing | 0.022 | N | 0.167 | neutral | N | 0.496541384 | None | None | N |
| T/P | 0.3452 | ambiguous | 0.2973 | benign | -0.192 | Destabilizing | 0.966 | D | 0.639 | neutral | N | 0.500090963 | None | None | N |
| T/Q | 0.2529 | likely_benign | 0.265 | benign | -0.506 | Destabilizing | 0.974 | D | 0.655 | neutral | None | None | None | None | N |
| T/R | 0.2625 | likely_benign | 0.2633 | benign | -0.35 | Destabilizing | 0.949 | D | 0.627 | neutral | None | None | None | None | N |
| T/S | 0.1174 | likely_benign | 0.1162 | benign | -0.903 | Destabilizing | 0.051 | N | 0.197 | neutral | N | 0.500907053 | None | None | N |
| T/V | 0.1133 | likely_benign | 0.1081 | benign | -0.192 | Destabilizing | 0.842 | D | 0.503 | neutral | None | None | None | None | N |
| T/W | 0.6389 | likely_pathogenic | 0.6328 | pathogenic | -0.673 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.3202 | likely_benign | 0.3202 | benign | -0.369 | Destabilizing | 0.991 | D | 0.711 | prob.delet. | 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.