Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| N2AB | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| N2A | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| N2B | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| Novex-1 | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| Novex-2 | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
| Novex-3 | 48 | 367;368;369 | chr2:178802291;178802290;178802289 | chr2:179667018;179667017;179667016 |
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/A | None | None | None | N | 0.091 | 0.13 | 0.0954503805726 | gnomAD-4.0.0 | 2.73628E-06 | None | None | None | 0.043(TCAP) | N | None | 2.98686E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79858E-06 | 0 | 1.65579E-05 |
| T/I | rs1295047971  |
-0.176 | 0.128 | N | 0.278 | 0.311 | 0.442363741745 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | -0.067(TCAP) | N | None | 0 | 0 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1295047971 |
-0.176 | 0.128 | N | 0.278 | 0.311 | 0.442363741745 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | -0.067(TCAP) | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | None | None | None | N | 0.154 | 0.256 | 0.183819452728 | gnomAD-4.0.0 | 6.84069E-07 | None | None | None | -0.021(TCAP) | N | None | 0 | 0 | None | 0 | 2.52029E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0802 | likely_benign | 0.1122 | benign | -0.484 | Destabilizing | None | N | 0.091 | neutral | N | 0.457250338 | None | 0.043(TCAP) | N |
| T/C | 0.8045 | likely_pathogenic | 0.9155 | pathogenic | -0.21 | Destabilizing | 0.674 | D | 0.349 | neutral | None | None | None | -0.026(TCAP) | N |
| T/D | 0.3939 | ambiguous | 0.6166 | pathogenic | 0.348 | Stabilizing | 0.077 | N | 0.283 | neutral | None | None | None | -0.166(TCAP) | N |
| T/E | 0.3027 | likely_benign | 0.4879 | ambiguous | 0.278 | Stabilizing | 0.103 | N | 0.283 | neutral | None | None | None | -0.259(TCAP) | N |
| T/F | 0.4131 | ambiguous | 0.6206 | pathogenic | -1.009 | Destabilizing | 0.881 | D | 0.408 | neutral | None | None | None | 0.073(TCAP) | N |
| T/G | 0.2527 | likely_benign | 0.3597 | ambiguous | -0.615 | Destabilizing | 0.126 | N | 0.284 | neutral | None | None | None | 0.061(TCAP) | N |
| T/H | 0.3588 | ambiguous | 0.5422 | ambiguous | -1.063 | Destabilizing | 0.735 | D | 0.353 | neutral | None | None | None | 0.564(TCAP) | N |
| T/I | 0.2762 | likely_benign | 0.4465 | ambiguous | -0.254 | Destabilizing | 0.128 | N | 0.278 | neutral | N | 0.498671488 | None | -0.067(TCAP) | N |
| T/K | 0.256 | likely_benign | 0.3773 | ambiguous | -0.269 | Destabilizing | 0.074 | N | 0.279 | neutral | None | None | None | -0.352(TCAP) | N |
| T/L | 0.1431 | likely_benign | 0.2217 | benign | -0.254 | Destabilizing | 0.074 | N | 0.293 | neutral | None | None | None | -0.067(TCAP) | N |
| T/M | 0.1432 | likely_benign | 0.2015 | benign | 0.077 | Stabilizing | 0.735 | D | 0.339 | neutral | None | None | None | 0.2(TCAP) | N |
| T/N | 0.1474 | likely_benign | 0.227 | benign | -0.053 | Destabilizing | 0.031 | N | 0.145 | neutral | N | 0.477395621 | None | -0.477(TCAP) | N |
| T/P | 0.0927 | likely_benign | 0.1328 | benign | -0.303 | Destabilizing | None | N | 0.154 | neutral | N | 0.428957535 | None | -0.021(TCAP) | N |
| T/Q | 0.2414 | likely_benign | 0.3528 | ambiguous | -0.295 | Destabilizing | 0.154 | N | 0.401 | neutral | None | None | None | -0.371(TCAP) | N |
| T/R | 0.2112 | likely_benign | 0.3283 | benign | -0.099 | Destabilizing | 0.51 | D | 0.359 | neutral | None | None | None | -0.433(TCAP) | N |
| T/S | 0.105 | likely_benign | 0.1447 | benign | -0.31 | Destabilizing | None | N | 0.1 | neutral | N | 0.470518563 | None | -0.25(TCAP) | N |
| T/V | 0.2044 | likely_benign | 0.3125 | benign | -0.303 | Destabilizing | 0.002 | N | 0.099 | neutral | None | None | None | -0.021(TCAP) | N |
| T/W | 0.7904 | likely_pathogenic | 0.913 | pathogenic | -0.98 | Destabilizing | 0.988 | D | 0.361 | neutral | None | None | None | 0.104(TCAP) | N |
| T/Y | 0.4763 | ambiguous | 0.6813 | pathogenic | -0.693 | Destabilizing | 0.958 | D | 0.393 | neutral | None | None | None | 0.288(TCAP) | 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.