Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22887 | 68884;68885;68886 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| N2AB | 21246 | 63961;63962;63963 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| N2A | 20319 | 61180;61181;61182 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| N2B | 13822 | 41689;41690;41691 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| Novex-1 | 13947 | 42064;42065;42066 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| Novex-2 | 14014 | 42265;42266;42267 | chr2:178577767;178577766;178577765 | chr2:179442494;179442493;179442492 |
| 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/F | rs2046762704  |
None | 0.295 | N | 0.363 | 0.138 | 0.404592120364 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/F | rs2046762704 |
None | 0.295 | N | 0.363 | 0.138 | 0.404592120364 | gnomAD-4.0.0 | 6.57903E-06 | None | None | None | None | N | None | 2.41441E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | None | None | None | N | 0.139 | 0.043 | 0.0138822411134 | gnomAD-4.0.0 | 2.05319E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69886E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0774 | likely_benign | 0.0704 | benign | -0.647 | Destabilizing | None | N | 0.127 | neutral | N | 0.469362277 | None | None | N |
| S/C | 0.1097 | likely_benign | 0.0999 | benign | -0.398 | Destabilizing | 0.295 | N | 0.302 | neutral | N | 0.492567211 | None | None | N |
| S/D | 0.2955 | likely_benign | 0.3106 | benign | 0.18 | Stabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| S/E | 0.3717 | ambiguous | 0.3753 | ambiguous | 0.123 | Stabilizing | 0.016 | N | 0.291 | neutral | None | None | None | None | N |
| S/F | 0.1737 | likely_benign | 0.146 | benign | -1.032 | Destabilizing | 0.295 | N | 0.363 | neutral | N | 0.511152972 | None | None | N |
| S/G | 0.0872 | likely_benign | 0.0778 | benign | -0.819 | Destabilizing | 0.031 | N | 0.286 | neutral | None | None | None | None | N |
| S/H | 0.2082 | likely_benign | 0.2095 | benign | -1.182 | Destabilizing | 0.628 | D | 0.306 | neutral | None | None | None | None | N |
| S/I | 0.1077 | likely_benign | 0.1039 | benign | -0.312 | Destabilizing | 0.038 | N | 0.371 | neutral | None | None | None | None | N |
| S/K | 0.4203 | ambiguous | 0.4254 | ambiguous | -0.626 | Destabilizing | 0.072 | N | 0.263 | neutral | None | None | None | None | N |
| S/L | 0.0949 | likely_benign | 0.083 | benign | -0.312 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| S/M | 0.1299 | likely_benign | 0.1127 | benign | -0.134 | Destabilizing | 0.356 | N | 0.307 | neutral | None | None | None | None | N |
| S/N | 0.0769 | likely_benign | 0.077 | benign | -0.368 | Destabilizing | 0.038 | N | 0.287 | neutral | None | None | None | None | N |
| S/P | 0.3648 | ambiguous | 0.3431 | ambiguous | -0.393 | Destabilizing | 0.106 | N | 0.333 | neutral | N | 0.480656706 | None | None | N |
| S/Q | 0.2912 | likely_benign | 0.2861 | benign | -0.555 | Destabilizing | 0.136 | N | 0.265 | neutral | None | None | None | None | N |
| S/R | 0.3902 | ambiguous | 0.4023 | ambiguous | -0.413 | Destabilizing | 0.072 | N | 0.319 | neutral | None | None | None | None | N |
| S/T | 0.0673 | likely_benign | 0.0596 | benign | -0.479 | Destabilizing | None | N | 0.139 | neutral | N | 0.391690927 | None | None | N |
| S/V | 0.1134 | likely_benign | 0.1052 | benign | -0.393 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| S/W | 0.2998 | likely_benign | 0.2782 | benign | -1.003 | Destabilizing | 0.864 | D | 0.39 | neutral | None | None | None | None | N |
| S/Y | 0.1373 | likely_benign | 0.1319 | benign | -0.754 | Destabilizing | 0.295 | N | 0.361 | neutral | N | 0.51879102 | 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.