Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35946 | 108061;108062;108063 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| N2AB | 34305 | 103138;103139;103140 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| N2A | 33378 | 100357;100358;100359 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| N2B | 26881 | 80866;80867;80868 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| Novex-1 | 27006 | 81241;81242;81243 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| Novex-2 | 27073 | 81442;81443;81444 | chr2:178527152;178527151;178527150 | chr2:179391879;179391878;179391877 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/P | rs281864931  |
-0.76 | 0.998 | D | 0.721 | 0.628 | 0.531873083431 |
Pollazzon (2010)
Rudloff (2015)
| None |
TMD 
LGMD2J
|
het | None | -1.036(OBSL1) -0.709(OBSCN) | N | Genetic analysis of TTN in single 3-generation ITA family; co-segregates with disease (n = 5, 5 affected (total 7)); Domain unfolds at body temperature; eliminates binding to OBSCN-Ig1; low expression; monomeric | None | None | None | None | None | None | None | None | None | None | None |
| H/Y | rs1686745897 |
None | 0.993 | N | 0.442 | 0.424 | 0.4744847356 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | -0.435(OBSL1) -0.23(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31868E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.5462 | ambiguous | 0.5654 | pathogenic | -0.607 | Destabilizing | 0.97 | D | 0.57 | neutral | None | None | None | -0.823(OBSL1) -0.495(OBSCN) | N |
| H/C | 0.3111 | likely_benign | 0.3099 | benign | -0.094 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | -0.981(OBSL1) -0.789(OBSCN) | N |
| H/D | 0.4279 | ambiguous | 0.457 | ambiguous | 0.015 | Stabilizing | 0.961 | D | 0.533 | neutral | N | 0.507641025 | None | -0.594(OBSL1) -0.406(OBSCN) | N |
| H/E | 0.4956 | ambiguous | 0.5171 | ambiguous | 0.074 | Stabilizing | 0.942 | D | 0.449 | neutral | None | None | None | -0.707(OBSL1) -0.499(OBSCN) | N |
| H/F | 0.4646 | ambiguous | 0.4795 | ambiguous | 0.28 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | -0.474(OBSL1) -0.19(OBSCN) | N |
| H/G | 0.6452 | likely_pathogenic | 0.6547 | pathogenic | -0.92 | Destabilizing | 0.985 | D | 0.597 | neutral | None | None | None | -0.726(OBSL1) -0.394(OBSCN) | N |
| H/I | 0.4435 | ambiguous | 0.4456 | ambiguous | 0.223 | Stabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | -1.15(OBSL1) -0.82(OBSCN) | N |
| H/K | 0.4469 | ambiguous | 0.4312 | ambiguous | -0.53 | Destabilizing | 0.942 | D | 0.53 | neutral | None | None | None | -1.175(OBSL1) -0.798(OBSCN) | N |
| H/L | 0.1855 | likely_benign | 0.1874 | benign | 0.223 | Stabilizing | 0.989 | D | 0.669 | neutral | N | 0.483129369 | None | -1.15(OBSL1) -0.82(OBSCN) | N |
| H/M | 0.6809 | likely_pathogenic | 0.6782 | pathogenic | 0.064 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | -1.328(OBSL1) -1.058(OBSCN) | N |
| H/N | 0.1978 | likely_benign | 0.2086 | benign | -0.517 | Destabilizing | 0.98 | D | 0.448 | neutral | N | 0.475451248 | None | -0.512(OBSL1) -0.46(OBSCN) | N |
| H/P | 0.7767 | likely_pathogenic | 0.7725 | pathogenic | -0.03 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | D | 0.532211395 | None | -1.036(OBSL1) -0.709(OBSCN) | N |
| H/Q | 0.2847 | likely_benign | 0.2883 | benign | -0.373 | Destabilizing | 0.689 | D | 0.238 | neutral | N | 0.424985143 | None | -0.603(OBSL1) -0.458(OBSCN) | N |
| H/R | 0.1596 | likely_benign | 0.1558 | benign | -0.863 | Destabilizing | 0.961 | D | 0.457 | neutral | N | 0.437202291 | None | -1.911(OBSL1) -1.653(OBSCN) | N |
| H/S | 0.3947 | ambiguous | 0.4103 | ambiguous | -0.692 | Destabilizing | 0.97 | D | 0.532 | neutral | None | None | None | -0.247(OBSL1) -0.05(OBSCN) | N |
| H/T | 0.4535 | ambiguous | 0.4695 | ambiguous | -0.528 | Destabilizing | 0.996 | D | 0.645 | neutral | None | None | None | -0.375(OBSL1) -0.161(OBSCN) | N |
| H/V | 0.408 | ambiguous | 0.4152 | ambiguous | -0.03 | Destabilizing | 0.996 | D | 0.725 | prob.delet. | None | None | None | -1.036(OBSL1) -0.709(OBSCN) | N |
| H/W | 0.5684 | likely_pathogenic | 0.5495 | ambiguous | 0.537 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | -0.402(OBSL1) -0.152(OBSCN) | N |
| H/Y | 0.1638 | likely_benign | 0.1657 | benign | 0.71 | Stabilizing | 0.993 | D | 0.442 | neutral | N | 0.511105404 | None | -0.435(OBSL1) -0.23(OBSCN) | 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.