Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27341 | 82246;82247;82248 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| N2AB | 25700 | 77323;77324;77325 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| N2A | 24773 | 74542;74543;74544 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| N2B | 18276 | 55051;55052;55053 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| Novex-1 | 18401 | 55426;55427;55428 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| Novex-2 | 18468 | 55627;55628;55629 | chr2:178564111;178564110;178564109 | chr2:179428838;179428837;179428836 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs555414240  |
0.088 | 1.0 | N | 0.698 | 0.358 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11321E-04 | None | 0 | None | 0 | 4.46E-05 | 0 |
| R/Q | rs555414240 |
0.088 | 1.0 | N | 0.698 | 0.358 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs555414240 |
0.088 | 1.0 | N | 0.698 | 0.358 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/Q | rs555414240 |
0.088 | 1.0 | N | 0.698 | 0.358 | None | gnomAD-4.0.0 | 2.41684E-05 | None | None | None | None | I | None | 1.33312E-05 | 0 | None | 0 | 8.91782E-05 | None | 0 | 1.65017E-04 | 2.3735E-05 | 3.29402E-05 | 3.20154E-05 |
| R/W | rs746488250 |
-0.499 | 1.0 | N | 0.748 | 0.38 | 0.326616659874 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| R/W | rs746488250 |
-0.499 | 1.0 | N | 0.748 | 0.38 | 0.326616659874 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs746488250 |
-0.499 | 1.0 | N | 0.748 | 0.38 | 0.326616659874 | gnomAD-4.0.0 | 2.04521E-05 | None | None | None | None | I | None | 2.6713E-05 | 1.66728E-05 | None | 0 | 4.45712E-05 | None | 0 | 0 | 1.94965E-05 | 3.29402E-05 | 3.20277E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8968 | likely_pathogenic | 0.9247 | pathogenic | -0.049 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| R/C | 0.4943 | ambiguous | 0.5624 | ambiguous | -0.305 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/D | 0.9855 | likely_pathogenic | 0.9896 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| R/E | 0.8956 | likely_pathogenic | 0.9197 | pathogenic | -0.099 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | I |
| R/F | 0.9381 | likely_pathogenic | 0.958 | pathogenic | -0.283 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/G | 0.8508 | likely_pathogenic | 0.8912 | pathogenic | -0.233 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.48897779 | None | None | I |
| R/H | 0.4302 | ambiguous | 0.4772 | ambiguous | -0.67 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| R/I | 0.7514 | likely_pathogenic | 0.8156 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/K | 0.3789 | ambiguous | 0.4116 | ambiguous | -0.198 | Destabilizing | 0.998 | D | 0.557 | neutral | None | None | None | None | I |
| R/L | 0.6664 | likely_pathogenic | 0.7591 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.585 | neutral | N | 0.451764867 | None | None | I |
| R/M | 0.847 | likely_pathogenic | 0.8879 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/N | 0.9646 | likely_pathogenic | 0.974 | pathogenic | -0.056 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
| R/P | 0.9161 | likely_pathogenic | 0.9293 | pathogenic | 0.269 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.51377391 | None | None | I |
| R/Q | 0.3428 | ambiguous | 0.3968 | ambiguous | -0.126 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | N | 0.463035948 | None | None | I |
| R/S | 0.9463 | likely_pathogenic | 0.9628 | pathogenic | -0.372 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| R/T | 0.8842 | likely_pathogenic | 0.9185 | pathogenic | -0.181 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | I |
| R/V | 0.8348 | likely_pathogenic | 0.8749 | pathogenic | 0.269 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| R/W | 0.5621 | ambiguous | 0.6518 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.748 | deleterious | N | 0.49787856 | None | None | I |
| R/Y | 0.8575 | likely_pathogenic | 0.8914 | pathogenic | 0.046 | Stabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | I |
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.