Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23272 | 70039;70040;70041 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| N2AB | 21631 | 65116;65117;65118 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| N2A | 20704 | 62335;62336;62337 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| N2B | 14207 | 42844;42845;42846 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| Novex-1 | 14332 | 43219;43220;43221 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| Novex-2 | 14399 | 43420;43421;43422 | chr2:178576318;178576317;178576316 | chr2:179441045;179441044;179441043 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/S | rs758398301  |
-2.705 | 0.994 | N | 0.829 | 0.567 | 0.798838478998 | gnomAD-2.1.1 | 9.61E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.05E-05 | 0 |
| I/S | rs758398301 |
-2.705 | 0.994 | N | 0.829 | 0.567 | 0.798838478998 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/S | rs758398301 |
-2.705 | 0.994 | N | 0.829 | 0.567 | 0.798838478998 | gnomAD-4.0.0 | 9.53922E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.71762E-04 | 1.11732E-05 | 0 | 1.64929E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9717 | likely_pathogenic | 0.9715 | pathogenic | -2.302 | Highly Destabilizing | 0.931 | D | 0.695 | prob.neutral | None | None | None | None | I |
| I/C | 0.9741 | likely_pathogenic | 0.9739 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| I/D | 0.9967 | likely_pathogenic | 0.9961 | pathogenic | -2.24 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | I |
| I/E | 0.9907 | likely_pathogenic | 0.9902 | pathogenic | -2.171 | Highly Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | I |
| I/F | 0.9273 | likely_pathogenic | 0.9216 | pathogenic | -1.541 | Destabilizing | 0.994 | D | 0.69 | prob.neutral | N | 0.513180517 | None | None | I |
| I/G | 0.993 | likely_pathogenic | 0.992 | pathogenic | -2.713 | Highly Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | I |
| I/H | 0.995 | likely_pathogenic | 0.9948 | pathogenic | -2.022 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| I/K | 0.9803 | likely_pathogenic | 0.9803 | pathogenic | -1.773 | Destabilizing | 0.999 | D | 0.833 | deleterious | None | None | None | None | I |
| I/L | 0.5178 | ambiguous | 0.5347 | ambiguous | -1.181 | Destabilizing | 0.689 | D | 0.438 | neutral | D | 0.522852832 | None | None | I |
| I/M | 0.5183 | ambiguous | 0.5355 | ambiguous | -0.849 | Destabilizing | 0.994 | D | 0.673 | neutral | D | 0.522463362 | None | None | I |
| I/N | 0.928 | likely_pathogenic | 0.9253 | pathogenic | -1.648 | Destabilizing | 0.998 | D | 0.847 | deleterious | N | 0.511956431 | None | None | I |
| I/P | 0.9661 | likely_pathogenic | 0.9655 | pathogenic | -1.529 | Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | I |
| I/Q | 0.99 | likely_pathogenic | 0.9899 | pathogenic | -1.768 | Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | I |
| I/R | 0.9823 | likely_pathogenic | 0.9809 | pathogenic | -1.172 | Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | I |
| I/S | 0.9731 | likely_pathogenic | 0.9697 | pathogenic | -2.261 | Highly Destabilizing | 0.994 | D | 0.829 | deleterious | N | 0.515968902 | None | None | I |
| I/T | 0.939 | likely_pathogenic | 0.9367 | pathogenic | -2.075 | Highly Destabilizing | 0.961 | D | 0.759 | deleterious | N | 0.504612597 | None | None | I |
| I/V | 0.1277 | likely_benign | 0.1261 | benign | -1.529 | Destabilizing | 0.122 | N | 0.237 | neutral | N | 0.449259151 | None | None | I |
| I/W | 0.9975 | likely_pathogenic | 0.9969 | pathogenic | -1.743 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| I/Y | 0.984 | likely_pathogenic | 0.9822 | pathogenic | -1.549 | Destabilizing | 0.999 | D | 0.815 | deleterious | 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.