Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4708 | 14347;14348;14349 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| N2AB | 4391 | 13396;13397;13398 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| N2A | 3464 | 10615;10616;10617 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| N2B | 4345 | 13258;13259;13260 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| Novex-1 | 4470 | 13633;13634;13635 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| Novex-2 | 4537 | 13834;13835;13836 | chr2:178738331;178738330;178738329 | chr2:179603058;179603057;179603056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 0.007 | N | 0.136 | 0.068 | 0.0846915920261 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| P/L | rs778412304  |
0.05 | 0.549 | N | 0.375 | 0.248 | None | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/L | rs778412304 |
0.05 | 0.549 | N | 0.375 | 0.248 | None | gnomAD-4.0.0 | 5.47686E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19902E-06 | 0 | 0 |
| P/T | None | None | 0.379 | N | 0.221 | 0.062 | 0.132336055621 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0924 | likely_benign | 0.1064 | benign | -0.577 | Destabilizing | 0.007 | N | 0.136 | neutral | N | 0.452069886 | None | None | N |
| P/C | 0.5546 | ambiguous | 0.6939 | pathogenic | -0.653 | Destabilizing | 0.992 | D | 0.411 | neutral | None | None | None | None | N |
| P/D | 0.3263 | likely_benign | 0.4142 | ambiguous | -0.365 | Destabilizing | 0.447 | N | 0.232 | neutral | None | None | None | None | N |
| P/E | 0.331 | likely_benign | 0.4361 | ambiguous | -0.449 | Destabilizing | 0.617 | D | 0.234 | neutral | None | None | None | None | N |
| P/F | 0.5912 | likely_pathogenic | 0.732 | pathogenic | -0.646 | Destabilizing | 0.92 | D | 0.421 | neutral | None | None | None | None | N |
| P/G | 0.2731 | likely_benign | 0.339 | benign | -0.751 | Destabilizing | 0.25 | N | 0.243 | neutral | None | None | None | None | N |
| P/H | 0.1718 | likely_benign | 0.2313 | benign | -0.247 | Destabilizing | 0.896 | D | 0.382 | neutral | N | 0.452546277 | None | None | N |
| P/I | 0.5615 | ambiguous | 0.6708 | pathogenic | -0.252 | Destabilizing | 0.92 | D | 0.435 | neutral | None | None | None | None | N |
| P/K | 0.4058 | ambiguous | 0.528 | ambiguous | -0.542 | Destabilizing | 0.447 | N | 0.229 | neutral | None | None | None | None | N |
| P/L | 0.2212 | likely_benign | 0.2982 | benign | -0.252 | Destabilizing | 0.549 | D | 0.375 | neutral | N | 0.432840179 | None | None | N |
| P/M | 0.4661 | ambiguous | 0.5768 | pathogenic | -0.401 | Destabilizing | 0.992 | D | 0.383 | neutral | None | None | None | None | N |
| P/N | 0.2273 | likely_benign | 0.2885 | benign | -0.297 | Destabilizing | 0.021 | N | 0.241 | neutral | None | None | None | None | N |
| P/Q | 0.2029 | likely_benign | 0.2696 | benign | -0.504 | Destabilizing | 0.85 | D | 0.35 | neutral | None | None | None | None | N |
| P/R | 0.2577 | likely_benign | 0.3673 | ambiguous | -0.033 | Destabilizing | 0.81 | D | 0.393 | neutral | N | 0.452003923 | None | None | N |
| P/S | 0.0921 | likely_benign | 0.1088 | benign | -0.685 | Destabilizing | 0.007 | N | 0.114 | neutral | N | 0.406897126 | None | None | N |
| P/T | 0.1335 | likely_benign | 0.1628 | benign | -0.661 | Destabilizing | 0.379 | N | 0.221 | neutral | N | 0.449868379 | None | None | N |
| P/V | 0.3962 | ambiguous | 0.4897 | ambiguous | -0.325 | Destabilizing | 0.617 | D | 0.363 | neutral | None | None | None | None | N |
| P/W | 0.7149 | likely_pathogenic | 0.8406 | pathogenic | -0.746 | Destabilizing | 0.992 | D | 0.55 | neutral | None | None | None | None | N |
| P/Y | 0.466 | ambiguous | 0.5979 | pathogenic | -0.447 | Destabilizing | 0.972 | D | 0.42 | 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.