Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35910 | 107953;107954;107955 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| N2AB | 34269 | 103030;103031;103032 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| N2A | 33342 | 100249;100250;100251 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| N2B | 26845 | 80758;80759;80760 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| Novex-1 | 26970 | 81133;81134;81135 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| Novex-2 | 27037 | 81334;81335;81336 | chr2:178527260;178527259;178527258 | chr2:179391987;179391986;179391985 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs370649675  |
0.199 | 0.98 | N | 0.422 | 0.302 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | -0.03(OBSL1) 0.032(OBSCN) | N | None | 1.29836E-04 | 2.92E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/K | rs370649675 |
0.199 | 0.98 | N | 0.422 | 0.302 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | -0.03(OBSL1) 0.032(OBSCN) | N | None | 1.2072E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/K | rs370649675 |
0.199 | 0.98 | N | 0.422 | 0.302 | None | 1000 genomes | 1.99681E-04 | None | None | None | -0.03(OBSL1) 0.032(OBSCN) | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| E/K | rs370649675 |
0.199 | 0.98 | N | 0.422 | 0.302 | None | gnomAD-4.0.0 | 6.82594E-06 | None | None | None | -0.03(OBSL1) 0.032(OBSCN) | N | None | 9.33806E-05 | 3.3399E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20657E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2054 | likely_benign | 0.2432 | benign | -0.681 | Destabilizing | 0.961 | D | 0.448 | neutral | N | 0.469351129 | None | -0.306(OBSL1) -0.262(OBSCN) | N |
| E/C | 0.9601 | likely_pathogenic | 0.9711 | pathogenic | -0.227 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | -0.319(OBSL1) -0.417(OBSCN) | N |
| E/D | 0.4512 | ambiguous | 0.5471 | ambiguous | -0.713 | Destabilizing | 0.954 | D | 0.408 | neutral | N | 0.499252749 | None | -0.524(OBSL1) -0.277(OBSCN) | N |
| E/F | 0.9588 | likely_pathogenic | 0.9689 | pathogenic | -0.218 | Destabilizing | 0.999 | D | 0.578 | neutral | None | None | None | -0.118(OBSL1) -0.105(OBSCN) | N |
| E/G | 0.4016 | ambiguous | 0.4438 | ambiguous | -0.986 | Destabilizing | 0.98 | D | 0.466 | neutral | N | 0.504959358 | None | -0.483(OBSL1) -0.433(OBSCN) | N |
| E/H | 0.8037 | likely_pathogenic | 0.8518 | pathogenic | -0.268 | Destabilizing | 0.999 | D | 0.413 | neutral | None | None | None | 0.544(OBSL1) 0.662(OBSCN) | N |
| E/I | 0.6269 | likely_pathogenic | 0.693 | pathogenic | 0.132 | Stabilizing | 0.999 | D | 0.565 | neutral | None | None | None | 0.209(OBSL1) 0.24(OBSCN) | N |
| E/K | 0.1774 | likely_benign | 0.1864 | benign | -0.009 | Destabilizing | 0.98 | D | 0.422 | neutral | N | 0.501348905 | None | -0.03(OBSL1) 0.032(OBSCN) | N |
| E/L | 0.7473 | likely_pathogenic | 0.8002 | pathogenic | 0.132 | Stabilizing | 0.996 | D | 0.495 | neutral | None | None | None | 0.209(OBSL1) 0.24(OBSCN) | N |
| E/M | 0.7138 | likely_pathogenic | 0.7558 | pathogenic | 0.409 | Stabilizing | 1.0 | D | 0.555 | neutral | None | None | None | 0.851(OBSL1) 0.825(OBSCN) | N |
| E/N | 0.6339 | likely_pathogenic | 0.7272 | pathogenic | -0.551 | Destabilizing | 0.999 | D | 0.409 | neutral | None | None | None | -1.517(OBSL1) -1.621(OBSCN) | N |
| E/P | 0.7801 | likely_pathogenic | 0.8522 | pathogenic | -0.117 | Destabilizing | 0.041 | N | 0.327 | neutral | None | None | None | 0.043(OBSL1) 0.078(OBSCN) | N |
| E/Q | 0.2257 | likely_benign | 0.2627 | benign | -0.452 | Destabilizing | 0.993 | D | 0.379 | neutral | N | 0.48058963 | None | -0.936(OBSL1) -1.021(OBSCN) | N |
| E/R | 0.3614 | ambiguous | 0.3848 | ambiguous | 0.241 | Stabilizing | 0.999 | D | 0.407 | neutral | None | None | None | -0.113(OBSL1) -0.003(OBSCN) | N |
| E/S | 0.4019 | ambiguous | 0.4886 | ambiguous | -0.763 | Destabilizing | 0.985 | D | 0.405 | neutral | None | None | None | -1.272(OBSL1) -1.355(OBSCN) | N |
| E/T | 0.4301 | ambiguous | 0.5001 | ambiguous | -0.503 | Destabilizing | 0.985 | D | 0.427 | neutral | None | None | None | -1.08(OBSL1) -1.171(OBSCN) | N |
| E/V | 0.4031 | ambiguous | 0.4561 | ambiguous | -0.117 | Destabilizing | 0.994 | D | 0.447 | neutral | N | 0.487590174 | None | 0.043(OBSL1) 0.078(OBSCN) | N |
| E/W | 0.9874 | likely_pathogenic | 0.9892 | pathogenic | 0.057 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | -0.282(OBSL1) -0.26(OBSCN) | N |
| E/Y | 0.9145 | likely_pathogenic | 0.934 | pathogenic | 0.059 | Stabilizing | 0.999 | D | 0.531 | neutral | None | None | None | -0.139(OBSL1) -0.149(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.