Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35907 | 107944;107945;107946 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| N2AB | 34266 | 103021;103022;103023 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| N2A | 33339 | 100240;100241;100242 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| N2B | 26842 | 80749;80750;80751 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| Novex-1 | 26967 | 81124;81125;81126 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| Novex-2 | 27034 | 81325;81326;81327 | chr2:178527269;178527268;178527267 | chr2:179391996;179391995;179391994 |
| 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/I | rs773833357  |
0.881 | 0.967 | N | 0.664 | 0.346 | 0.623070239186 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | -0.659(OBSL1) 0.03(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 9.91E-05 | None | 0 | 0 | 0 |
| S/I | rs773833357 |
0.881 | 0.967 | N | 0.664 | 0.346 | 0.623070239186 | gnomAD-4.0.0 | 8.02409E-06 | None | None | None | -0.659(OBSL1) 0.03(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 7.2015E-05 | 0 |
| S/R | rs977991321 |
-0.37 | 0.967 | N | 0.649 | 0.306 | 0.426904299391 | gnomAD-2.1.1 | 7.2E-06 | None | None | None | -1.399(OBSL1) -0.013(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.58E-05 | 0 |
| S/R | rs977991321 |
-0.37 | 0.967 | N | 0.649 | 0.306 | 0.426904299391 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -1.399(OBSL1) -0.013(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs977991321 |
-0.37 | 0.967 | N | 0.649 | 0.306 | 0.426904299391 | gnomAD-4.0.0 | 9.32589E-06 | None | None | None | -1.399(OBSL1) -0.013(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.19055E-05 | 0 | 1.60658E-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 | 0.13 | likely_benign | 0.1241 | benign | -0.493 | Destabilizing | 0.693 | D | 0.357 | neutral | None | None | None | -0.72(OBSL1) -0.002(OBSCN) | N |
| S/C | 0.1971 | likely_benign | 0.1989 | benign | -0.279 | Destabilizing | 0.999 | D | 0.603 | neutral | N | 0.504597187 | None | -0.318(OBSL1) 0.043(OBSCN) | N |
| S/D | 0.6533 | likely_pathogenic | 0.6236 | pathogenic | -0.12 | Destabilizing | 0.916 | D | 0.491 | neutral | None | None | None | -0.162(OBSL1) -0.487(OBSCN) | N |
| S/E | 0.6893 | likely_pathogenic | 0.6764 | pathogenic | -0.14 | Destabilizing | 0.916 | D | 0.493 | neutral | None | None | None | -0.167(OBSL1) -0.519(OBSCN) | N |
| S/F | 0.3378 | likely_benign | 0.3151 | benign | -0.678 | Destabilizing | 0.987 | D | 0.655 | neutral | None | None | None | -0.747(OBSL1) -0.113(OBSCN) | N |
| S/G | 0.2575 | likely_benign | 0.232 | benign | -0.732 | Destabilizing | 0.892 | D | 0.406 | neutral | N | 0.485478974 | None | -0.763(OBSL1) -0.026(OBSCN) | N |
| S/H | 0.4925 | ambiguous | 0.475 | ambiguous | -1.218 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | -0.811(OBSL1) 0.656(OBSCN) | N |
| S/I | 0.2757 | likely_benign | 0.269 | benign | 0.029 | Stabilizing | 0.967 | D | 0.664 | neutral | N | 0.496002666 | None | -0.659(OBSL1) 0.03(OBSCN) | N |
| S/K | 0.8692 | likely_pathogenic | 0.8536 | pathogenic | -0.737 | Destabilizing | 0.916 | D | 0.489 | neutral | None | None | None | -1.16(OBSL1) -0.106(OBSCN) | N |
| S/L | 0.1742 | likely_benign | 0.1706 | benign | 0.029 | Stabilizing | 0.845 | D | 0.538 | neutral | None | None | None | -0.659(OBSL1) 0.03(OBSCN) | N |
| S/M | 0.3579 | ambiguous | 0.35 | ambiguous | 0.215 | Stabilizing | 0.997 | D | 0.599 | neutral | None | None | None | -0.464(OBSL1) 0.509(OBSCN) | N |
| S/N | 0.2799 | likely_benign | 0.2616 | benign | -0.57 | Destabilizing | 0.892 | D | 0.502 | neutral | N | 0.51181748 | None | -0.2(OBSL1) -0.506(OBSCN) | N |
| S/P | 0.7121 | likely_pathogenic | 0.6168 | pathogenic | -0.11 | Destabilizing | 0.987 | D | 0.641 | neutral | None | None | None | -0.667(OBSL1) 0.027(OBSCN) | N |
| S/Q | 0.6723 | likely_pathogenic | 0.6555 | pathogenic | -0.688 | Destabilizing | 0.987 | D | 0.61 | neutral | None | None | None | -0.301(OBSL1) -0.406(OBSCN) | N |
| S/R | 0.7419 | likely_pathogenic | 0.7114 | pathogenic | -0.613 | Destabilizing | 0.967 | D | 0.649 | neutral | N | 0.514876428 | None | -1.399(OBSL1) -0.013(OBSCN) | N |
| S/T | 0.1171 | likely_benign | 0.1169 | benign | -0.571 | Destabilizing | 0.025 | N | 0.311 | neutral | N | 0.443898977 | None | -0.706(OBSL1) -0.356(OBSCN) | N |
| S/V | 0.2965 | likely_benign | 0.2948 | benign | -0.11 | Destabilizing | 0.95 | D | 0.599 | neutral | None | None | None | -0.667(OBSL1) 0.027(OBSCN) | N |
| S/W | 0.5083 | ambiguous | 0.4822 | ambiguous | -0.72 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | -1.241(OBSL1) -0.173(OBSCN) | N |
| S/Y | 0.3064 | likely_benign | 0.2838 | benign | -0.456 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | -0.79(OBSL1) 0.067(OBSCN) | 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.