Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28829 | 86710;86711;86712 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| N2AB | 27188 | 81787;81788;81789 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| N2A | 26261 | 79006;79007;79008 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| N2B | 19764 | 59515;59516;59517 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| Novex-1 | 19889 | 59890;59891;59892 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| Novex-2 | 19956 | 60091;60092;60093 | chr2:178559647;178559646;178559645 | chr2:179424374;179424373;179424372 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs371485481  |
-0.962 | 0.996 | N | 0.522 | 0.588 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66223E-04 |
| N/D | rs371485481 |
-0.962 | 0.996 | N | 0.522 | 0.588 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/D | rs371485481 |
-0.962 | 0.996 | N | 0.522 | 0.588 | None | gnomAD-4.0.0 | 2.47904E-06 | None | None | None | None | I | None | 1.33494E-05 | 5.00167E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | None | None | 1.0 | N | 0.699 | 0.631 | 0.325263233342 | gnomAD-4.0.0 | 2.05289E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9838 | likely_pathogenic | 0.9822 | pathogenic | -0.741 | Destabilizing | 0.994 | D | 0.576 | neutral | None | None | None | None | I |
| N/C | 0.9428 | likely_pathogenic | 0.9366 | pathogenic | 0.006 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| N/D | 0.9283 | likely_pathogenic | 0.9226 | pathogenic | -1.009 | Destabilizing | 0.996 | D | 0.522 | neutral | N | 0.511606674 | None | None | I |
| N/E | 0.9932 | likely_pathogenic | 0.9928 | pathogenic | -0.947 | Destabilizing | 0.997 | D | 0.58 | neutral | None | None | None | None | I |
| N/F | 0.999 | likely_pathogenic | 0.999 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| N/G | 0.9303 | likely_pathogenic | 0.9267 | pathogenic | -1.038 | Destabilizing | 0.997 | D | 0.483 | neutral | None | None | None | None | I |
| N/H | 0.9125 | likely_pathogenic | 0.9014 | pathogenic | -0.996 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.517647061 | None | None | I |
| N/I | 0.9939 | likely_pathogenic | 0.9934 | pathogenic | -0.003 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | D | 0.5246485 | None | None | I |
| N/K | 0.9953 | likely_pathogenic | 0.9949 | pathogenic | -0.294 | Destabilizing | 0.996 | D | 0.594 | neutral | D | 0.535244337 | None | None | I |
| N/L | 0.9835 | likely_pathogenic | 0.9826 | pathogenic | -0.003 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| N/M | 0.9871 | likely_pathogenic | 0.9867 | pathogenic | 0.598 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| N/P | 0.9948 | likely_pathogenic | 0.9949 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| N/Q | 0.9929 | likely_pathogenic | 0.9923 | pathogenic | -1.032 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| N/R | 0.9939 | likely_pathogenic | 0.9936 | pathogenic | -0.259 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| N/S | 0.6018 | likely_pathogenic | 0.5803 | pathogenic | -0.823 | Destabilizing | 0.905 | D | 0.303 | neutral | N | 0.473232117 | None | None | I |
| N/T | 0.8734 | likely_pathogenic | 0.8501 | pathogenic | -0.593 | Destabilizing | 0.992 | D | 0.546 | neutral | N | 0.511860163 | None | None | I |
| N/V | 0.9897 | likely_pathogenic | 0.9886 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| N/W | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -0.555 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/Y | 0.9812 | likely_pathogenic | 0.9796 | pathogenic | -0.307 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.535751316 | 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.