Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35941 | 108046;108047;108048 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| N2AB | 34300 | 103123;103124;103125 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| N2A | 33373 | 100342;100343;100344 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| N2B | 26876 | 80851;80852;80853 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| Novex-1 | 27001 | 81226;81227;81228 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| Novex-2 | 27068 | 81427;81428;81429 | chr2:178527167;178527166;178527165 | chr2:179391894;179391893;179391892 |
| 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/Q | rs777087450  |
-0.719 | 0.891 | N | 0.359 | 0.185 | 0.299427821978 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | -2.328(OBSL1) -1.419(OBSCN) | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| E/Q | rs777087450 |
-0.719 | 0.891 | N | 0.359 | 0.185 | 0.299427821978 | gnomAD-4.0.0 | 6.36361E-06 | None | None | None | -2.328(OBSL1) -1.419(OBSCN) | N | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 1.88253E-05 | 0 | 5.71507E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1498 | likely_benign | 0.1574 | benign | -0.473 | Destabilizing | 0.454 | N | 0.344 | neutral | N | 0.4812625 | None | -2.267(OBSL1) -0.838(OBSCN) | N |
| E/C | 0.8115 | likely_pathogenic | 0.8049 | pathogenic | -0.135 | Destabilizing | 0.998 | D | 0.399 | neutral | None | None | None | -2.427(OBSL1) -1.186(OBSCN) | N |
| E/D | 0.0983 | likely_benign | 0.1048 | benign | -0.423 | Destabilizing | 0.005 | N | 0.202 | neutral | N | 0.464850253 | None | -1.68(OBSL1) -0.7(OBSCN) | N |
| E/F | 0.6862 | likely_pathogenic | 0.6879 | pathogenic | -0.282 | Destabilizing | 0.991 | D | 0.357 | neutral | None | None | None | -2.195(OBSL1) -1.031(OBSCN) | N |
| E/G | 0.1152 | likely_benign | 0.1142 | benign | -0.713 | Destabilizing | 0.005 | N | 0.251 | neutral | N | 0.515492504 | None | -2.29(OBSL1) -0.972(OBSCN) | N |
| E/H | 0.3647 | ambiguous | 0.3519 | ambiguous | -0.286 | Destabilizing | 0.991 | D | 0.301 | neutral | None | None | None | -1.398(OBSL1) 0.248(OBSCN) | N |
| E/I | 0.3732 | ambiguous | 0.3769 | ambiguous | 0.14 | Stabilizing | 0.974 | D | 0.363 | neutral | None | None | None | -2.188(OBSL1) -0.455(OBSCN) | N |
| E/K | 0.1347 | likely_benign | 0.1273 | benign | -0.02 | Destabilizing | 0.801 | D | 0.348 | neutral | N | 0.502408563 | None | -2.499(OBSL1) -0.724(OBSCN) | N |
| E/L | 0.3622 | ambiguous | 0.3651 | ambiguous | 0.14 | Stabilizing | 0.974 | D | 0.361 | neutral | None | None | None | -2.188(OBSL1) -0.455(OBSCN) | N |
| E/M | 0.4601 | ambiguous | 0.4615 | ambiguous | 0.298 | Stabilizing | 0.998 | D | 0.359 | neutral | None | None | None | -1.714(OBSL1) 0.369(OBSCN) | N |
| E/N | 0.1781 | likely_benign | 0.1841 | benign | -0.247 | Destabilizing | 0.728 | D | 0.316 | neutral | None | None | None | -2.22(OBSL1) -1.766(OBSCN) | N |
| E/P | 0.3488 | ambiguous | 0.3675 | ambiguous | -0.044 | Destabilizing | 0.974 | D | 0.329 | neutral | None | None | None | -2.215(OBSL1) -0.576(OBSCN) | N |
| E/Q | 0.121 | likely_benign | 0.116 | benign | -0.184 | Destabilizing | 0.891 | D | 0.359 | neutral | N | 0.504102074 | None | -2.328(OBSL1) -1.419(OBSCN) | N |
| E/R | 0.2125 | likely_benign | 0.1993 | benign | 0.184 | Stabilizing | 0.974 | D | 0.324 | neutral | None | None | None | -2.146(OBSL1) -0.462(OBSCN) | N |
| E/S | 0.1638 | likely_benign | 0.1658 | benign | -0.459 | Destabilizing | 0.842 | D | 0.352 | neutral | None | None | None | -2.599(OBSL1) -1.794(OBSCN) | N |
| E/T | 0.208 | likely_benign | 0.2112 | benign | -0.27 | Destabilizing | 0.842 | D | 0.344 | neutral | None | None | None | -2.62(OBSL1) -1.678(OBSCN) | N |
| E/V | 0.2182 | likely_benign | 0.2216 | benign | -0.044 | Destabilizing | 0.966 | D | 0.338 | neutral | N | 0.503448713 | None | -2.215(OBSL1) -0.576(OBSCN) | N |
| E/W | 0.822 | likely_pathogenic | 0.8256 | pathogenic | -0.128 | Destabilizing | 0.998 | D | 0.461 | neutral | None | None | None | -2.036(OBSL1) -1.219(OBSCN) | N |
| E/Y | 0.5188 | ambiguous | 0.5193 | ambiguous | -0.056 | Destabilizing | 0.991 | D | 0.352 | neutral | None | None | None | -2.06(OBSL1) -0.993(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.