Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19722 | 59389;59390;59391 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| N2AB | 18081 | 54466;54467;54468 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| N2A | 17154 | 51685;51686;51687 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| N2B | 10657 | 32194;32195;32196 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| Novex-1 | 10782 | 32569;32570;32571 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| Novex-2 | 10849 | 32770;32771;32772 | chr2:178592955;178592954;178592953 | chr2:179457682;179457681;179457680 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs116592778  |
-0.728 | 0.001 | N | 0.141 | 0.126 | None | gnomAD-2.1.1 | 1.2615E-03 | None | None | None | None | N | None | 1.29371E-02 | 7.07294E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.61E-05 | 5.61956E-04 |
| V/A | rs116592778 |
-0.728 | 0.001 | N | 0.141 | 0.126 | None | gnomAD-3.1.2 | 3.80926E-03 | None | None | None | None | N | None | 1.31388E-02 | 1.18079E-03 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 5.26316E-03 |
| V/A | rs116592778 |
-0.728 | 0.001 | N | 0.141 | 0.126 | None | 1000 genomes | 4.39297E-03 | None | None | None | None | N | None | 1.66E-02 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/A | rs116592778 |
-0.728 | 0.001 | N | 0.141 | 0.126 | None | gnomAD-4.0.0 | 7.04069E-04 | None | None | None | None | N | None | 1.29508E-02 | 8.16993E-04 | None | 6.7595E-05 | 0 | None | 0 | 8.25355E-04 | 3.56052E-05 | 0 | 1.07255E-03 |
| V/G | None | None | 0.201 | N | 0.445 | 0.268 | 0.538237646413 | gnomAD-4.0.0 | 6.84293E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99573E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0753 | likely_benign | 0.0753 | benign | -1.282 | Destabilizing | 0.001 | N | 0.141 | neutral | N | 0.414276999 | None | None | N |
| V/C | 0.6396 | likely_pathogenic | 0.6514 | pathogenic | -0.836 | Destabilizing | 0.977 | D | 0.374 | neutral | None | None | None | None | N |
| V/D | 0.1687 | likely_benign | 0.1439 | benign | -1.086 | Destabilizing | 0.81 | D | 0.489 | neutral | N | 0.478192404 | None | None | N |
| V/E | 0.1419 | likely_benign | 0.1287 | benign | -1.134 | Destabilizing | 0.617 | D | 0.483 | neutral | None | None | None | None | N |
| V/F | 0.203 | likely_benign | 0.193 | benign | -1.098 | Destabilizing | 0.896 | D | 0.394 | neutral | N | 0.519887098 | None | None | N |
| V/G | 0.1578 | likely_benign | 0.1492 | benign | -1.541 | Destabilizing | 0.201 | N | 0.445 | neutral | N | 0.464687176 | None | None | N |
| V/H | 0.4493 | ambiguous | 0.441 | ambiguous | -0.993 | Destabilizing | 0.992 | D | 0.483 | neutral | None | None | None | None | N |
| V/I | 0.0739 | likely_benign | 0.0799 | benign | -0.697 | Destabilizing | 0.334 | N | 0.29 | neutral | N | 0.471613149 | None | None | N |
| V/K | 0.2887 | likely_benign | 0.2745 | benign | -1.109 | Destabilizing | 0.617 | D | 0.481 | neutral | None | None | None | None | N |
| V/L | 0.1549 | likely_benign | 0.1731 | benign | -0.697 | Destabilizing | 0.201 | N | 0.31 | neutral | N | 0.415431792 | None | None | N |
| V/M | 0.1229 | likely_benign | 0.1336 | benign | -0.504 | Destabilizing | 0.972 | D | 0.356 | neutral | None | None | None | None | N |
| V/N | 0.172 | likely_benign | 0.1672 | benign | -0.831 | Destabilizing | 0.85 | D | 0.499 | neutral | None | None | None | None | N |
| V/P | 0.1849 | likely_benign | 0.2105 | benign | -0.857 | Destabilizing | 0.92 | D | 0.477 | neutral | None | None | None | None | N |
| V/Q | 0.236 | likely_benign | 0.2335 | benign | -1.066 | Destabilizing | 0.92 | D | 0.496 | neutral | None | None | None | None | N |
| V/R | 0.2989 | likely_benign | 0.2728 | benign | -0.483 | Destabilizing | 0.85 | D | 0.509 | neutral | None | None | None | None | N |
| V/S | 0.1188 | likely_benign | 0.1162 | benign | -1.29 | Destabilizing | 0.059 | N | 0.295 | neutral | None | None | None | None | N |
| V/T | 0.0937 | likely_benign | 0.0935 | benign | -1.235 | Destabilizing | 0.4 | N | 0.235 | neutral | None | None | None | None | N |
| V/W | 0.7493 | likely_pathogenic | 0.7355 | pathogenic | -1.215 | Destabilizing | 0.992 | D | 0.561 | neutral | None | None | None | None | N |
| V/Y | 0.4769 | ambiguous | 0.4541 | ambiguous | -0.954 | Destabilizing | 0.972 | D | 0.384 | 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.