Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29123 | 87592;87593;87594 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| N2AB | 27482 | 82669;82670;82671 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| N2A | 26555 | 79888;79889;79890 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| N2B | 20058 | 60397;60398;60399 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| Novex-1 | 20183 | 60772;60773;60774 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| Novex-2 | 20250 | 60973;60974;60975 | chr2:178557987;178557986;178557985 | chr2:179422714;179422713;179422712 |
| 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/G | rs375198596  |
-0.736 | 0.071 | N | 0.254 | 0.142 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs375198596 |
-0.736 | 0.071 | N | 0.254 | 0.142 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs375198596 |
-0.736 | 0.071 | N | 0.254 | 0.142 | None | gnomAD-4.0.0 | 6.56996E-06 | None | None | None | None | I | None | 2.41231E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs375198596 |
0.025 | 0.977 | N | 0.446 | 0.242 | 0.290962096972 | gnomAD-2.1.1 | 1.00026E-04 | None | None | None | None | I | None | 4.13E-05 | 1.1309E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.64145E-04 | 1.40371E-04 |
| S/R | rs375198596 |
0.025 | 0.977 | N | 0.446 | 0.242 | 0.290962096972 | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | I | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.76362E-04 | 0 | 0 |
| S/R | rs375198596 |
0.025 | 0.977 | N | 0.446 | 0.242 | 0.290962096972 | gnomAD-4.0.0 | 1.08454E-04 | None | None | None | None | I | None | 2.66902E-05 | 8.33278E-05 | None | 0 | 0 | None | 0 | 0 | 1.33913E-04 | 7.68488E-05 | 4.80307E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0752 | likely_benign | 0.0705 | benign | -0.258 | Destabilizing | 0.931 | D | 0.419 | neutral | None | None | None | None | I |
| S/C | 0.0665 | likely_benign | 0.0641 | benign | -0.267 | Destabilizing | 1.0 | D | 0.556 | neutral | N | 0.517436731 | None | None | I |
| S/D | 0.717 | likely_pathogenic | 0.7464 | pathogenic | -0.056 | Destabilizing | 0.942 | D | 0.354 | neutral | None | None | None | None | I |
| S/E | 0.7659 | likely_pathogenic | 0.7775 | pathogenic | -0.171 | Destabilizing | 0.97 | D | 0.366 | neutral | None | None | None | None | I |
| S/F | 0.2515 | likely_benign | 0.2462 | benign | -1.045 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | I |
| S/G | 0.1041 | likely_benign | 0.1096 | benign | -0.275 | Destabilizing | 0.071 | N | 0.254 | neutral | N | 0.478878343 | None | None | I |
| S/H | 0.4389 | ambiguous | 0.4389 | ambiguous | -0.7 | Destabilizing | 0.996 | D | 0.515 | neutral | None | None | None | None | I |
| S/I | 0.1704 | likely_benign | 0.1799 | benign | -0.338 | Destabilizing | 0.998 | D | 0.63 | neutral | N | 0.47277909 | None | None | I |
| S/K | 0.8119 | likely_pathogenic | 0.8284 | pathogenic | -0.326 | Destabilizing | 0.304 | N | 0.31 | neutral | None | None | None | None | I |
| S/L | 0.1206 | likely_benign | 0.1151 | benign | -0.338 | Destabilizing | 0.985 | D | 0.558 | neutral | None | None | None | None | I |
| S/M | 0.242 | likely_benign | 0.2334 | benign | -0.121 | Destabilizing | 1.0 | D | 0.529 | neutral | None | None | None | None | I |
| S/N | 0.2254 | likely_benign | 0.2507 | benign | -0.064 | Destabilizing | 0.248 | N | 0.313 | neutral | N | 0.446421994 | None | None | I |
| S/P | 0.7951 | likely_pathogenic | 0.7697 | pathogenic | -0.291 | Destabilizing | 0.999 | D | 0.488 | neutral | None | None | None | None | I |
| S/Q | 0.627 | likely_pathogenic | 0.6284 | pathogenic | -0.313 | Destabilizing | 0.991 | D | 0.418 | neutral | None | None | None | None | I |
| S/R | 0.678 | likely_pathogenic | 0.7086 | pathogenic | -0.13 | Destabilizing | 0.977 | D | 0.446 | neutral | N | 0.479918493 | None | None | I |
| S/T | 0.103 | likely_benign | 0.1037 | benign | -0.181 | Destabilizing | 0.961 | D | 0.413 | neutral | N | 0.485822958 | None | None | I |
| S/V | 0.1623 | likely_benign | 0.1617 | benign | -0.291 | Destabilizing | 0.996 | D | 0.58 | neutral | None | None | None | None | I |
| S/W | 0.467 | ambiguous | 0.4469 | ambiguous | -1.118 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| S/Y | 0.2704 | likely_benign | 0.2641 | benign | -0.811 | Destabilizing | 0.999 | D | 0.639 | neutral | 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.