Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28953 | 87082;87083;87084 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| N2AB | 27312 | 82159;82160;82161 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| N2A | 26385 | 79378;79379;79380 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| N2B | 19888 | 59887;59888;59889 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| Novex-1 | 20013 | 60262;60263;60264 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| Novex-2 | 20080 | 60463;60464;60465 | chr2:178558602;178558601;178558600 | chr2:179423329;179423328;179423327 |
| 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/G | rs748750008  |
-0.594 | None | N | 0.055 | 0.062 | 0.185906805712 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 8.78E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs748750008 |
-0.594 | None | N | 0.055 | 0.062 | 0.185906805712 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs748750008 |
-0.594 | None | N | 0.055 | 0.062 | 0.185906805712 | gnomAD-4.0.0 | 3.84841E-06 | None | None | None | None | N | None | 0 | 5.09909E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1183912804 |
None | None | N | 0.045 | 0.062 | 0.171388866994 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| S/R | rs748750008 |
0.139 | 0.055 | N | 0.45 | 0.122 | 0.231873229951 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.32E-05 | None | 0 | 0 | 0 |
| S/R | rs748750008 |
0.139 | 0.055 | N | 0.45 | 0.122 | 0.231873229951 | gnomAD-4.0.0 | 3.18808E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85987E-06 | 1.44317E-05 | 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 | 0.0705 | likely_benign | 0.0758 | benign | -0.513 | Destabilizing | 0.007 | N | 0.207 | neutral | None | None | None | None | N |
| S/C | 0.0926 | likely_benign | 0.0901 | benign | -0.313 | Destabilizing | 0.828 | D | 0.373 | neutral | N | 0.478765525 | None | None | N |
| S/D | 0.1379 | likely_benign | 0.1408 | benign | 0.628 | Stabilizing | None | N | 0.053 | neutral | None | None | None | None | N |
| S/E | 0.2339 | likely_benign | 0.2367 | benign | 0.549 | Stabilizing | 0.016 | N | 0.267 | neutral | None | None | None | None | N |
| S/F | 0.1707 | likely_benign | 0.2035 | benign | -1.115 | Destabilizing | 0.628 | D | 0.445 | neutral | None | None | None | None | N |
| S/G | 0.0636 | likely_benign | 0.0663 | benign | -0.625 | Destabilizing | None | N | 0.055 | neutral | N | 0.480981993 | None | None | N |
| S/H | 0.1666 | likely_benign | 0.1694 | benign | -1.152 | Destabilizing | 0.214 | N | 0.422 | neutral | None | None | None | None | N |
| S/I | 0.1487 | likely_benign | 0.1558 | benign | -0.343 | Destabilizing | 0.295 | N | 0.469 | neutral | N | 0.499954543 | None | None | N |
| S/K | 0.3465 | ambiguous | 0.3615 | ambiguous | -0.233 | Destabilizing | 0.016 | N | 0.245 | neutral | None | None | None | None | N |
| S/L | 0.1185 | likely_benign | 0.1359 | benign | -0.343 | Destabilizing | 0.072 | N | 0.426 | neutral | None | None | None | None | N |
| S/M | 0.1624 | likely_benign | 0.1817 | benign | -0.107 | Destabilizing | 0.628 | D | 0.383 | neutral | None | None | None | None | N |
| S/N | 0.0716 | likely_benign | 0.074 | benign | -0.014 | Destabilizing | None | N | 0.045 | neutral | N | 0.448426858 | None | None | N |
| S/P | 0.7451 | likely_pathogenic | 0.7727 | pathogenic | -0.372 | Destabilizing | 0.136 | N | 0.453 | neutral | None | None | None | None | N |
| S/Q | 0.2455 | likely_benign | 0.2475 | benign | -0.223 | Destabilizing | 0.072 | N | 0.307 | neutral | None | None | None | None | N |
| S/R | 0.3046 | likely_benign | 0.3092 | benign | -0.16 | Destabilizing | 0.055 | N | 0.45 | neutral | N | 0.473055943 | None | None | N |
| S/T | 0.0736 | likely_benign | 0.0804 | benign | -0.176 | Destabilizing | 0.012 | N | 0.282 | neutral | N | 0.489582834 | None | None | N |
| S/V | 0.1383 | likely_benign | 0.1458 | benign | -0.372 | Destabilizing | 0.136 | N | 0.448 | neutral | None | None | None | None | N |
| S/W | 0.3097 | likely_benign | 0.3401 | ambiguous | -1.079 | Destabilizing | 0.864 | D | 0.435 | neutral | None | None | None | None | N |
| S/Y | 0.1453 | likely_benign | 0.1611 | benign | -0.792 | Destabilizing | 0.628 | D | 0.445 | neutral | 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.