Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15914 | 47965;47966;47967 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| N2AB | 14273 | 43042;43043;43044 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| N2A | 13346 | 40261;40262;40263 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| N2B | 6849 | 20770;20771;20772 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| Novex-1 | 6974 | 21145;21146;21147 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| Novex-2 | 7041 | 21346;21347;21348 | chr2:178617345;178617344;178617343 | chr2:179482072;179482071;179482070 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | rs2154208656  |
None | 0.669 | N | 0.499 | 0.265 | 0.754467340223 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| V/G | rs2154208656 |
None | 0.669 | N | 0.499 | 0.265 | 0.754467340223 | gnomAD-4.0.0 | 1.26437E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.5671E-07 | 1.18483E-05 | 0 |
| V/L | rs764059405 |
-0.174 | 0.625 | N | 0.407 | 0.199 | 0.48102604628 | gnomAD-2.1.1 | 5.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.09952E-04 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs764059405 |
-0.174 | 0.625 | N | 0.407 | 0.199 | 0.48102604628 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94628E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs764059405 |
-0.174 | 0.625 | N | 0.407 | 0.199 | 0.48102604628 | gnomAD-4.0.0 | 2.52919E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.0876E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2362 | likely_benign | 0.2604 | benign | -1.56 | Destabilizing | 0.005 | N | 0.167 | neutral | N | 0.471760314 | None | None | N |
| V/C | 0.5786 | likely_pathogenic | 0.5761 | pathogenic | -0.881 | Destabilizing | 0.007 | N | 0.243 | neutral | None | None | None | None | N |
| V/D | 0.6049 | likely_pathogenic | 0.6519 | pathogenic | -2.15 | Highly Destabilizing | 0.966 | D | 0.562 | neutral | N | 0.510625313 | None | None | N |
| V/E | 0.4759 | ambiguous | 0.5358 | ambiguous | -1.914 | Destabilizing | 0.949 | D | 0.551 | neutral | None | None | None | None | N |
| V/F | 0.2631 | likely_benign | 0.289 | benign | -0.904 | Destabilizing | 0.989 | D | 0.528 | neutral | N | 0.477798823 | None | None | N |
| V/G | 0.3894 | ambiguous | 0.4308 | ambiguous | -2.098 | Highly Destabilizing | 0.669 | D | 0.499 | neutral | N | 0.454664117 | None | None | N |
| V/H | 0.587 | likely_pathogenic | 0.632 | pathogenic | -2.038 | Highly Destabilizing | 0.998 | D | 0.575 | neutral | None | None | None | None | N |
| V/I | 0.1037 | likely_benign | 0.1113 | benign | -0.065 | Destabilizing | 0.625 | D | 0.457 | neutral | N | 0.4606868 | None | None | N |
| V/K | 0.5153 | ambiguous | 0.5723 | pathogenic | -1.176 | Destabilizing | 0.949 | D | 0.551 | neutral | None | None | None | None | N |
| V/L | 0.2704 | likely_benign | 0.3013 | benign | -0.065 | Destabilizing | 0.625 | D | 0.407 | neutral | N | 0.482403351 | None | None | N |
| V/M | 0.2662 | likely_benign | 0.2968 | benign | -0.079 | Destabilizing | 0.991 | D | 0.492 | neutral | None | None | None | None | N |
| V/N | 0.3832 | ambiguous | 0.475 | ambiguous | -1.551 | Destabilizing | 0.974 | D | 0.565 | neutral | None | None | None | None | N |
| V/P | 0.8254 | likely_pathogenic | 0.81 | pathogenic | -0.536 | Destabilizing | 0.974 | D | 0.559 | neutral | None | None | None | None | N |
| V/Q | 0.3955 | ambiguous | 0.4568 | ambiguous | -1.34 | Destabilizing | 0.974 | D | 0.563 | neutral | None | None | None | None | N |
| V/R | 0.4335 | ambiguous | 0.4702 | ambiguous | -1.187 | Destabilizing | 0.974 | D | 0.566 | neutral | None | None | None | None | N |
| V/S | 0.2493 | likely_benign | 0.3193 | benign | -2.118 | Highly Destabilizing | 0.728 | D | 0.486 | neutral | None | None | None | None | N |
| V/T | 0.2835 | likely_benign | 0.3415 | ambiguous | -1.737 | Destabilizing | 0.842 | D | 0.415 | neutral | None | None | None | None | N |
| V/W | 0.8959 | likely_pathogenic | 0.9035 | pathogenic | -1.512 | Destabilizing | 0.998 | D | 0.6 | neutral | None | None | None | None | N |
| V/Y | 0.6182 | likely_pathogenic | 0.6419 | pathogenic | -1.011 | Destabilizing | 0.991 | D | 0.519 | 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.