Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23169 | 69730;69731;69732 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| N2AB | 21528 | 64807;64808;64809 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| N2A | 20601 | 62026;62027;62028 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| N2B | 14104 | 42535;42536;42537 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| Novex-1 | 14229 | 42910;42911;42912 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| Novex-2 | 14296 | 43111;43112;43113 | chr2:178576739;178576738;178576737 | chr2:179441466;179441465;179441464 |
| 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/I | rs879245080  |
None | 0.782 | N | 0.691 | 0.392 | None | gnomAD-4.0.0 | 4.79005E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29696E-06 | 0 | 0 |
| S/N | None | None | 0.505 | N | 0.678 | 0.281 | 0.243972157842 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79913E-06 | 0 | 0 |
| S/R | None | None | 0.82 | N | 0.655 | 0.244 | 0.254761474806 | gnomAD-4.0.0 | 6.84303E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99577E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1362 | likely_benign | 0.1224 | benign | -0.548 | Destabilizing | 0.218 | N | 0.563 | neutral | None | None | None | None | I |
| S/C | 0.0921 | likely_benign | 0.0815 | benign | -0.392 | Destabilizing | 0.003 | N | 0.462 | neutral | N | 0.480602404 | None | None | I |
| S/D | 0.8161 | likely_pathogenic | 0.857 | pathogenic | -0.552 | Destabilizing | 0.575 | D | 0.656 | neutral | None | None | None | None | I |
| S/E | 0.8774 | likely_pathogenic | 0.894 | pathogenic | -0.615 | Destabilizing | 0.404 | N | 0.644 | neutral | None | None | None | None | I |
| S/F | 0.517 | ambiguous | 0.5504 | ambiguous | -1.012 | Destabilizing | 0.906 | D | 0.707 | prob.neutral | None | None | None | None | I |
| S/G | 0.2219 | likely_benign | 0.2093 | benign | -0.713 | Destabilizing | 0.505 | D | 0.585 | neutral | N | 0.467526762 | None | None | I |
| S/H | 0.6126 | likely_pathogenic | 0.6753 | pathogenic | -1.297 | Destabilizing | 0.973 | D | 0.64 | neutral | None | None | None | None | I |
| S/I | 0.501 | ambiguous | 0.5531 | ambiguous | -0.227 | Destabilizing | 0.782 | D | 0.691 | prob.neutral | N | 0.503857993 | None | None | I |
| S/K | 0.94 | likely_pathogenic | 0.9541 | pathogenic | -0.698 | Destabilizing | 0.004 | N | 0.434 | neutral | None | None | None | None | I |
| S/L | 0.2254 | likely_benign | 0.2059 | benign | -0.227 | Destabilizing | 0.404 | N | 0.623 | neutral | None | None | None | None | I |
| S/M | 0.3357 | likely_benign | 0.3379 | benign | 0.244 | Stabilizing | 0.991 | D | 0.641 | neutral | None | None | None | None | I |
| S/N | 0.2639 | likely_benign | 0.303 | benign | -0.542 | Destabilizing | 0.505 | D | 0.678 | prob.neutral | N | 0.493324608 | None | None | I |
| S/P | 0.9825 | likely_pathogenic | 0.9854 | pathogenic | -0.304 | Destabilizing | 0.906 | D | 0.658 | neutral | None | None | None | None | I |
| S/Q | 0.7658 | likely_pathogenic | 0.8014 | pathogenic | -0.867 | Destabilizing | 0.826 | D | 0.655 | neutral | None | None | None | None | I |
| S/R | 0.8854 | likely_pathogenic | 0.9119 | pathogenic | -0.44 | Destabilizing | 0.82 | D | 0.655 | neutral | N | 0.490473771 | None | None | I |
| S/T | 0.1979 | likely_benign | 0.1839 | benign | -0.573 | Destabilizing | 0.505 | D | 0.614 | neutral | N | 0.478258546 | None | None | I |
| S/V | 0.4066 | ambiguous | 0.4182 | ambiguous | -0.304 | Destabilizing | 0.404 | N | 0.673 | neutral | None | None | None | None | I |
| S/W | 0.6484 | likely_pathogenic | 0.6856 | pathogenic | -0.979 | Destabilizing | 0.991 | D | 0.727 | prob.delet. | None | None | None | None | I |
| S/Y | 0.4693 | ambiguous | 0.5207 | ambiguous | -0.71 | Destabilizing | 0.967 | D | 0.709 | prob.delet. | 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.