Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35972 | 108139;108140;108141 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| N2AB | 34331 | 103216;103217;103218 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| N2A | 33404 | 100435;100436;100437 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| N2B | 26907 | 80944;80945;80946 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| Novex-1 | 27032 | 81319;81320;81321 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| Novex-2 | 27099 | 81520;81521;81522 | chr2:178527074;178527073;178527072 | chr2:179391801;179391800;179391799 |
| 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 | rs397517478  |
-0.108 | 0.213 | N | 0.607 | 0.245 | None | gnomAD-2.1.1 | 7.85E-05 | None | None | None | -0.652(OBSL1) -0.28(OBSCN) | N | None | 4.13E-05 | 0 | None | 0 | 5.12E-05 | None | 9.81E-05 | None | 0 | 1.01311E-04 | 5.6164E-04 |
| S/I | rs397517478 |
-0.108 | 0.213 | N | 0.607 | 0.245 | None | gnomAD-3.1.2 | 1.18304E-04 | None | None | None | -0.652(OBSL1) -0.28(OBSCN) | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92308E-04 | None | 0 | 0 | 2.35218E-04 | 0 | 0 |
| S/I | rs397517478 |
-0.108 | 0.213 | N | 0.607 | 0.245 | None | gnomAD-4.0.0 | 7.93177E-05 | None | None | None | -0.652(OBSL1) -0.28(OBSCN) | N | None | 4.00449E-05 | 0 | None | 0 | 2.22747E-05 | None | 0 | 2.30112E-03 | 6.69577E-05 | 2.41562E-04 | 1.44078E-04 |
| S/N | None | None | 0.001 | N | 0.197 | 0.103 | 0.193865811164 | gnomAD-4.0.0 | 6.84175E-07 | None | None | None | -0.447(OBSL1) -0.887(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9942E-07 | 0 | 0 |
| S/R | None | None | 0.101 | N | 0.471 | 0.222 | 0.200317383148 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | -1.147(OBSL1) -0.943(OBSCN) | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.1221 | likely_benign | 0.1228 | benign | -1.036 | Destabilizing | 0.061 | N | 0.345 | neutral | None | None | None | -0.397(OBSL1) -0.033(OBSCN) | N |
| S/C | 0.1379 | likely_benign | 0.1408 | benign | -0.883 | Destabilizing | 0.978 | D | 0.522 | neutral | N | 0.500659124 | None | -0.386(OBSL1) -0.584(OBSCN) | N |
| S/D | 0.4392 | ambiguous | 0.4538 | ambiguous | -0.75 | Destabilizing | 0.129 | N | 0.409 | neutral | None | None | None | -0.033(OBSL1) -0.24(OBSCN) | N |
| S/E | 0.4514 | ambiguous | 0.4402 | ambiguous | -0.713 | Destabilizing | 0.004 | N | 0.235 | neutral | None | None | None | -0.122(OBSL1) -0.372(OBSCN) | N |
| S/F | 0.2191 | likely_benign | 0.2306 | benign | -1.307 | Destabilizing | 0.836 | D | 0.581 | neutral | None | None | None | -0.73(OBSL1) -0.27(OBSCN) | N |
| S/G | 0.1831 | likely_benign | 0.1827 | benign | -1.293 | Destabilizing | 0.101 | N | 0.405 | neutral | N | 0.518994169 | None | -0.327(OBSL1) 0.029(OBSCN) | N |
| S/H | 0.2007 | likely_benign | 0.2088 | benign | -1.745 | Destabilizing | 0.836 | D | 0.53 | neutral | None | None | None | -0.525(OBSL1) 0.421(OBSCN) | N |
| S/I | 0.1617 | likely_benign | 0.1611 | benign | -0.441 | Destabilizing | 0.213 | N | 0.607 | neutral | N | 0.418003242 | None | -0.652(OBSL1) -0.28(OBSCN) | N |
| S/K | 0.5101 | ambiguous | 0.5111 | ambiguous | -0.662 | Destabilizing | 0.001 | N | 0.187 | neutral | None | None | None | -0.898(OBSL1) -0.974(OBSCN) | N |
| S/L | 0.1404 | likely_benign | 0.141 | benign | -0.441 | Destabilizing | 0.129 | N | 0.497 | neutral | None | None | None | -0.652(OBSL1) -0.28(OBSCN) | N |
| S/M | 0.2248 | likely_benign | 0.2216 | benign | -0.128 | Destabilizing | 0.836 | D | 0.528 | neutral | None | None | None | -0.532(OBSL1) -0.038(OBSCN) | N |
| S/N | 0.1532 | likely_benign | 0.1606 | benign | -0.826 | Destabilizing | 0.001 | N | 0.197 | neutral | N | 0.432644621 | None | -0.447(OBSL1) -0.887(OBSCN) | N |
| S/P | 0.9667 | likely_pathogenic | 0.9633 | pathogenic | -0.608 | Destabilizing | 0.593 | D | 0.534 | neutral | None | None | None | -0.561(OBSL1) -0.189(OBSCN) | N |
| S/Q | 0.3564 | ambiguous | 0.3556 | ambiguous | -0.987 | Destabilizing | 0.418 | N | 0.513 | neutral | None | None | None | -0.441(OBSL1) -0.814(OBSCN) | N |
| S/R | 0.3594 | ambiguous | 0.3675 | ambiguous | -0.602 | Destabilizing | 0.101 | N | 0.471 | neutral | N | 0.434202059 | None | -1.147(OBSL1) -0.943(OBSCN) | N |
| S/T | 0.0834 | likely_benign | 0.0844 | benign | -0.811 | Destabilizing | 0.001 | N | 0.248 | neutral | N | 0.376212548 | None | -0.631(OBSL1) -0.828(OBSCN) | N |
| S/V | 0.2046 | likely_benign | 0.2099 | benign | -0.608 | Destabilizing | 0.264 | N | 0.541 | neutral | None | None | None | -0.561(OBSL1) -0.189(OBSCN) | N |
| S/W | 0.3685 | ambiguous | 0.3653 | ambiguous | -1.253 | Destabilizing | 0.983 | D | 0.596 | neutral | None | None | None | -0.884(OBSL1) -0.338(OBSCN) | N |
| S/Y | 0.1877 | likely_benign | 0.1917 | benign | -0.958 | Destabilizing | 0.94 | D | 0.591 | neutral | None | None | None | -0.671(OBSL1) -0.097(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.