Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19542 | 58849;58850;58851 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| N2AB | 17901 | 53926;53927;53928 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| N2A | 16974 | 51145;51146;51147 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| N2B | 10477 | 31654;31655;31656 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| Novex-1 | 10602 | 32029;32030;32031 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| Novex-2 | 10669 | 32230;32231;32232 | chr2:178593676;178593675;178593674 | chr2:179458403;179458402;179458401 |
| 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/P | rs145198325  |
-0.208 | None | N | 0.215 | 0.108 | None | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 1.93773E-04 | 8.72E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/P | rs145198325 |
-0.208 | None | N | 0.215 | 0.108 | None | gnomAD-3.1.2 | 1.05213E-04 | None | None | None | None | N | None | 3.61934E-04 | 0 | 1.09649E-03 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs145198325 |
-0.208 | None | N | 0.215 | 0.108 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/P | rs145198325 |
-0.208 | None | N | 0.215 | 0.108 | None | gnomAD-4.0.0 | 1.98349E-05 | None | None | None | None | N | None | 3.59904E-04 | 6.67223E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | None | None | 0.295 | D | 0.519 | 0.312 | 0.666034180468 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.077 | likely_benign | 0.0703 | benign | -0.196 | Destabilizing | 0.005 | N | 0.239 | neutral | N | 0.501050621 | None | None | N |
| S/C | 0.1286 | likely_benign | 0.1129 | benign | -0.337 | Destabilizing | 0.612 | D | 0.465 | neutral | N | 0.517982943 | None | None | N |
| S/D | 0.5486 | ambiguous | 0.4756 | ambiguous | 0.304 | Stabilizing | 0.031 | N | 0.341 | neutral | None | None | None | None | N |
| S/E | 0.5106 | ambiguous | 0.4311 | ambiguous | 0.258 | Stabilizing | 0.031 | N | 0.342 | neutral | None | None | None | None | N |
| S/F | 0.259 | likely_benign | 0.2173 | benign | -0.609 | Destabilizing | 0.295 | N | 0.52 | neutral | N | 0.501570696 | None | None | N |
| S/G | 0.103 | likely_benign | 0.0999 | benign | -0.368 | Destabilizing | 0.031 | N | 0.329 | neutral | None | None | None | None | N |
| S/H | 0.3351 | likely_benign | 0.2712 | benign | -0.76 | Destabilizing | 0.628 | D | 0.486 | neutral | None | None | None | None | N |
| S/I | 0.191 | likely_benign | 0.1718 | benign | 0.129 | Stabilizing | 0.038 | N | 0.549 | neutral | None | None | None | None | N |
| S/K | 0.6582 | likely_pathogenic | 0.5636 | ambiguous | -0.431 | Destabilizing | 0.031 | N | 0.333 | neutral | None | None | None | None | N |
| S/L | 0.103 | likely_benign | 0.0921 | benign | 0.129 | Stabilizing | 0.038 | N | 0.443 | neutral | None | None | None | None | N |
| S/M | 0.1809 | likely_benign | 0.1703 | benign | 0.015 | Stabilizing | 0.356 | N | 0.487 | neutral | None | None | None | None | N |
| S/N | 0.1696 | likely_benign | 0.1506 | benign | -0.29 | Destabilizing | 0.072 | N | 0.337 | neutral | None | None | None | None | N |
| S/P | 0.0514 | likely_benign | 0.0485 | benign | 0.053 | Stabilizing | None | N | 0.215 | neutral | N | 0.418818814 | None | None | N |
| S/Q | 0.3528 | ambiguous | 0.2856 | benign | -0.403 | Destabilizing | 0.136 | N | 0.408 | neutral | None | None | None | None | N |
| S/R | 0.6194 | likely_pathogenic | 0.5226 | ambiguous | -0.292 | Destabilizing | 0.072 | N | 0.489 | neutral | None | None | None | None | N |
| S/T | 0.0846 | likely_benign | 0.0789 | benign | -0.324 | Destabilizing | None | N | 0.115 | neutral | N | 0.431841252 | None | None | N |
| S/V | 0.1735 | likely_benign | 0.1512 | benign | 0.053 | Stabilizing | 0.038 | N | 0.454 | neutral | None | None | None | None | N |
| S/W | 0.3394 | likely_benign | 0.2872 | benign | -0.693 | Destabilizing | 0.864 | D | 0.561 | neutral | None | None | None | None | N |
| S/Y | 0.2097 | likely_benign | 0.1797 | benign | -0.372 | Destabilizing | 0.295 | N | 0.519 | neutral | D | 0.523562121 | 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.