Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24793 | 74602;74603;74604 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| N2AB | 23152 | 69679;69680;69681 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| N2A | 22225 | 66898;66899;66900 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| N2B | 15728 | 47407;47408;47409 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| Novex-1 | 15853 | 47782;47783;47784 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| Novex-2 | 15920 | 47983;47984;47985 | chr2:178571755;178571754;178571753 | chr2:179436482;179436481;179436480 |
| 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/L | rs766741890  |
-0.033 | 0.213 | N | 0.387 | 0.373 | None | gnomAD-2.1.1 | 3.23E-05 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 5.35E-05 | 0 |
| S/L | rs766741890 |
-0.033 | 0.213 | N | 0.387 | 0.373 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/L | rs766741890 |
-0.033 | 0.213 | N | 0.387 | 0.373 | None | gnomAD-4.0.0 | 1.79762E-05 | None | None | None | None | I | None | 1.33576E-05 | 3.33467E-05 | None | 0 | 0 | None | 0 | 1.6469E-04 | 1.78039E-05 | 0 | 6.40615E-05 |
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 | 0.066 | likely_benign | 0.0691 | benign | -0.19 | Destabilizing | 0.047 | N | 0.331 | neutral | N | 0.499525761 | None | None | I |
| S/C | 0.1238 | likely_benign | 0.1312 | benign | -0.455 | Destabilizing | 0.005 | N | 0.331 | neutral | None | None | None | None | I |
| S/D | 0.3707 | ambiguous | 0.43 | ambiguous | -0.137 | Destabilizing | 0.418 | N | 0.289 | neutral | None | None | None | None | I |
| S/E | 0.4711 | ambiguous | 0.5217 | ambiguous | -0.248 | Destabilizing | 0.418 | N | 0.311 | neutral | None | None | None | None | I |
| S/F | 0.2039 | likely_benign | 0.2059 | benign | -0.955 | Destabilizing | 0.836 | D | 0.392 | neutral | None | None | None | None | I |
| S/G | 0.0849 | likely_benign | 0.0877 | benign | -0.211 | Destabilizing | 0.228 | N | 0.33 | neutral | None | None | None | None | I |
| S/H | 0.3192 | likely_benign | 0.358 | ambiguous | -0.523 | Destabilizing | 0.94 | D | 0.354 | neutral | None | None | None | None | I |
| S/I | 0.1103 | likely_benign | 0.1121 | benign | -0.26 | Destabilizing | 0.557 | D | 0.401 | neutral | None | None | None | None | I |
| S/K | 0.5164 | ambiguous | 0.576 | pathogenic | -0.454 | Destabilizing | 0.01 | N | 0.212 | neutral | None | None | None | None | I |
| S/L | 0.0795 | likely_benign | 0.0824 | benign | -0.26 | Destabilizing | 0.213 | N | 0.387 | neutral | N | 0.489863974 | None | None | I |
| S/M | 0.1463 | likely_benign | 0.1491 | benign | -0.215 | Destabilizing | 0.836 | D | 0.352 | neutral | None | None | None | None | I |
| S/N | 0.1094 | likely_benign | 0.1216 | benign | -0.242 | Destabilizing | 0.418 | N | 0.311 | neutral | None | None | None | None | I |
| S/P | 0.1784 | likely_benign | 0.1734 | benign | -0.215 | Destabilizing | 0.002 | N | 0.215 | neutral | N | 0.4988724 | None | None | I |
| S/Q | 0.4157 | ambiguous | 0.4663 | ambiguous | -0.466 | Destabilizing | 0.716 | D | 0.311 | neutral | None | None | None | None | I |
| S/R | 0.4768 | ambiguous | 0.5245 | ambiguous | -0.204 | Destabilizing | 0.264 | N | 0.349 | neutral | None | None | None | None | I |
| S/T | 0.0614 | likely_benign | 0.0588 | benign | -0.351 | Destabilizing | 0.001 | N | 0.117 | neutral | D | 0.52240262 | None | None | I |
| S/V | 0.1128 | likely_benign | 0.1173 | benign | -0.215 | Destabilizing | 0.264 | N | 0.399 | neutral | None | None | None | None | I |
| S/W | 0.4324 | ambiguous | 0.4351 | ambiguous | -1.048 | Destabilizing | 0.983 | D | 0.413 | neutral | None | None | None | None | I |
| S/Y | 0.2254 | likely_benign | 0.2265 | benign | -0.736 | Destabilizing | 0.94 | D | 0.389 | 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.