Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19559 | 58900;58901;58902 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| N2AB | 17918 | 53977;53978;53979 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| N2A | 16991 | 51196;51197;51198 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| N2B | 10494 | 31705;31706;31707 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| Novex-1 | 10619 | 32080;32081;32082 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| Novex-2 | 10686 | 32281;32282;32283 | chr2:178593625;178593624;178593623 | chr2:179458352;179458351;179458350 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | None | None | 0.136 | N | 0.253 | 0.035 | 0.413761986042 | gnomAD-4.0.0 | 6.84595E-07 | None | None | None | None | I | None | 2.98954E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/Q | rs76604657  |
-0.209 | 0.966 | N | 0.49 | 0.382 | None | gnomAD-2.1.1 | 1.43533E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.07987E-03 | None | 0 | None | 0 | 0 | 0 |
| L/Q | rs76604657 |
-0.209 | 0.966 | N | 0.49 | 0.382 | None | gnomAD-3.1.2 | 1.18315E-04 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.48567E-03 | None | 0 | 0 | 0 | 0 | 0 |
| L/Q | rs76604657 |
-0.209 | 0.966 | N | 0.49 | 0.382 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| L/Q | rs76604657 |
-0.209 | 0.966 | N | 0.49 | 0.382 | None | gnomAD-4.0.0 | 1.76068E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.34358E-03 | None | 0 | 0 | 0 | 0 | 1.60169E-05 |
| L/V | None | None | 0.454 | N | 0.359 | 0.087 | 0.459463830659 | gnomAD-4.0.0 | 6.84595E-07 | None | None | None | None | I | None | 0 | 0 | None | 3.82848E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1955 | likely_benign | 0.1911 | benign | -0.601 | Destabilizing | 0.525 | D | 0.361 | neutral | None | None | None | None | I |
| L/C | 0.5036 | ambiguous | 0.4919 | ambiguous | -0.821 | Destabilizing | 0.998 | D | 0.364 | neutral | None | None | None | None | I |
| L/D | 0.6121 | likely_pathogenic | 0.595 | pathogenic | 0.027 | Stabilizing | 0.949 | D | 0.513 | neutral | None | None | None | None | I |
| L/E | 0.3388 | likely_benign | 0.3267 | benign | -0.047 | Destabilizing | 0.949 | D | 0.511 | neutral | None | None | None | None | I |
| L/F | 0.2056 | likely_benign | 0.1856 | benign | -0.581 | Destabilizing | 0.949 | D | 0.278 | neutral | None | None | None | None | I |
| L/G | 0.4974 | ambiguous | 0.4933 | ambiguous | -0.75 | Destabilizing | 0.949 | D | 0.491 | neutral | None | None | None | None | I |
| L/H | 0.2501 | likely_benign | 0.2283 | benign | 0.037 | Stabilizing | 0.998 | D | 0.477 | neutral | None | None | None | None | I |
| L/I | 0.0764 | likely_benign | 0.0749 | benign | -0.328 | Destabilizing | 0.067 | N | 0.103 | neutral | None | None | None | None | I |
| L/K | 0.2572 | likely_benign | 0.2559 | benign | -0.311 | Destabilizing | 0.949 | D | 0.473 | neutral | None | None | None | None | I |
| L/M | 0.1145 | likely_benign | 0.1098 | benign | -0.554 | Destabilizing | 0.136 | N | 0.253 | neutral | N | 0.425782071 | None | None | I |
| L/N | 0.3073 | likely_benign | 0.3162 | benign | -0.216 | Destabilizing | 0.949 | D | 0.511 | neutral | None | None | None | None | I |
| L/P | 0.2479 | likely_benign | 0.2842 | benign | -0.388 | Destabilizing | 0.966 | D | 0.506 | neutral | N | 0.435305632 | None | None | I |
| L/Q | 0.1522 | likely_benign | 0.1423 | benign | -0.373 | Destabilizing | 0.966 | D | 0.49 | neutral | N | 0.40940711 | None | None | I |
| L/R | 0.2138 | likely_benign | 0.1974 | benign | 0.181 | Stabilizing | 0.966 | D | 0.503 | neutral | N | 0.40652152 | None | None | I |
| L/S | 0.2566 | likely_benign | 0.2439 | benign | -0.699 | Destabilizing | 0.728 | D | 0.481 | neutral | None | None | None | None | I |
| L/T | 0.1754 | likely_benign | 0.1725 | benign | -0.658 | Destabilizing | 0.067 | N | 0.291 | neutral | None | None | None | None | I |
| L/V | 0.087 | likely_benign | 0.0854 | benign | -0.388 | Destabilizing | 0.454 | N | 0.359 | neutral | N | 0.42043218 | None | None | I |
| L/W | 0.3601 | ambiguous | 0.3203 | benign | -0.582 | Destabilizing | 0.998 | D | 0.541 | neutral | None | None | None | None | I |
| L/Y | 0.3855 | ambiguous | 0.3595 | ambiguous | -0.35 | Destabilizing | 0.974 | D | 0.366 | neutral | None | None | None | None | I |
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.