Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22514 | 67765;67766;67767 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| N2AB | 20873 | 62842;62843;62844 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| N2A | 19946 | 60061;60062;60063 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| N2B | 13449 | 40570;40571;40572 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| Novex-1 | 13574 | 40945;40946;40947 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| Novex-2 | 13641 | 41146;41147;41148 | chr2:178579657;178579656;178579655 | chr2:179444384;179444383;179444382 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs544847834  |
-0.294 | None | N | 0.158 | 0.055 | 0.0551355673512 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.67654E-04 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs544847834 |
-0.294 | None | N | 0.158 | 0.055 | 0.0551355673512 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.88048E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs544847834 |
-0.294 | None | N | 0.158 | 0.055 | 0.0551355673512 | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| T/I | rs544847834 |
-0.294 | None | N | 0.158 | 0.055 | 0.0551355673512 | gnomAD-4.0.0 | 4.33885E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11657E-04 | None | 0 | 0 | 0 | 0 | 3.20225E-05 |
| T/S | rs561270636 |
-1.001 | None | N | 0.133 | 0.057 | 0.0482279557977 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| T/S | rs561270636 |
-1.001 | None | N | 0.133 | 0.057 | 0.0482279557977 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| T/S | rs561270636 |
-1.001 | None | N | 0.133 | 0.057 | 0.0482279557977 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| T/S | rs561270636 |
-1.001 | None | N | 0.133 | 0.057 | 0.0482279557977 | gnomAD-4.0.0 | 3.09914E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.49004E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.076 | likely_benign | 0.0744 | benign | -0.776 | Destabilizing | 0.005 | N | 0.21 | neutral | N | 0.483310222 | None | None | N |
| T/C | 0.3271 | likely_benign | 0.3015 | benign | -0.46 | Destabilizing | 0.676 | D | 0.422 | neutral | None | None | None | None | N |
| T/D | 0.2609 | likely_benign | 0.2803 | benign | 0.343 | Stabilizing | 0.016 | N | 0.357 | neutral | None | None | None | None | N |
| T/E | 0.1423 | likely_benign | 0.1521 | benign | 0.316 | Stabilizing | 0.001 | N | 0.194 | neutral | None | None | None | None | N |
| T/F | 0.1814 | likely_benign | 0.2053 | benign | -1.087 | Destabilizing | 0.214 | N | 0.513 | neutral | None | None | None | None | N |
| T/G | 0.2036 | likely_benign | 0.2051 | benign | -0.971 | Destabilizing | 0.016 | N | 0.329 | neutral | None | None | None | None | N |
| T/H | 0.1665 | likely_benign | 0.1702 | benign | -1.141 | Destabilizing | 0.001 | N | 0.224 | neutral | None | None | None | None | N |
| T/I | 0.0775 | likely_benign | 0.086 | benign | -0.363 | Destabilizing | None | N | 0.158 | neutral | N | 0.441444957 | None | None | N |
| T/K | 0.0839 | likely_benign | 0.09 | benign | -0.446 | Destabilizing | None | N | 0.114 | neutral | None | None | None | None | N |
| T/L | 0.0638 | likely_benign | 0.0671 | benign | -0.363 | Destabilizing | 0.006 | N | 0.354 | neutral | None | None | None | None | N |
| T/M | 0.0739 | likely_benign | 0.0787 | benign | -0.198 | Destabilizing | 0.214 | N | 0.441 | neutral | None | None | None | None | N |
| T/N | 0.1054 | likely_benign | 0.112 | benign | -0.338 | Destabilizing | None | N | 0.164 | neutral | N | 0.464263102 | None | None | N |
| T/P | 0.1434 | likely_benign | 0.1388 | benign | -0.47 | Destabilizing | 0.106 | N | 0.463 | neutral | N | 0.468534855 | None | None | N |
| T/Q | 0.1165 | likely_benign | 0.1223 | benign | -0.487 | Destabilizing | 0.038 | N | 0.467 | neutral | None | None | None | None | N |
| T/R | 0.0862 | likely_benign | 0.0962 | benign | -0.2 | Destabilizing | 0.038 | N | 0.391 | neutral | None | None | None | None | N |
| T/S | 0.1006 | likely_benign | 0.0986 | benign | -0.665 | Destabilizing | None | N | 0.133 | neutral | N | 0.460684079 | None | None | N |
| T/V | 0.0736 | likely_benign | 0.0746 | benign | -0.47 | Destabilizing | None | N | 0.108 | neutral | None | None | None | None | N |
| T/W | 0.4146 | ambiguous | 0.4742 | ambiguous | -1.019 | Destabilizing | 0.864 | D | 0.458 | neutral | None | None | None | None | N |
| T/Y | 0.2328 | likely_benign | 0.2372 | benign | -0.766 | Destabilizing | 0.12 | N | 0.523 | 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.