Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24163 | 72712;72713;72714 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| N2AB | 22522 | 67789;67790;67791 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| N2A | 21595 | 65008;65009;65010 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| N2B | 15098 | 45517;45518;45519 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| Novex-1 | 15223 | 45892;45893;45894 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| Novex-2 | 15290 | 46093;46094;46095 | chr2:178573645;178573644;178573643 | chr2:179438372;179438371;179438370 |
| 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/C | rs778284888  |
-1.685 | 1.0 | N | 0.795 | 0.415 | 0.709351898144 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.87687E-04 | 0 | 0 |
| R/C | rs778284888 |
-1.685 | 1.0 | N | 0.795 | 0.415 | 0.709351898144 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93648E-04 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| R/C | rs778284888 |
-1.685 | 1.0 | N | 0.795 | 0.415 | 0.709351898144 | gnomAD-4.0.0 | 1.39829E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.5901E-05 | None | 1.66141E-05 | 0 | 1.33022E-05 | 2.87002E-05 | 1.73503E-05 |
| R/G | None | None | 0.954 | N | 0.643 | 0.509 | 0.691025755046 | gnomAD-4.0.0 | 7.40859E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.01654E-05 | 0 | 0 | 0 | 0 |
| R/H | rs374712231 |
-2.46 | 0.997 | N | 0.595 | 0.573 | None | gnomAD-2.1.1 | 3.48E-05 | None | None | None | None | N | None | 8.64E-05 | 0 | None | 0 | 6.07E-05 | None | 7.27E-05 | None | 0 | 3.01E-05 | 0 |
| R/H | rs374712231 |
-2.46 | 0.997 | N | 0.595 | 0.573 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 3.87297E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/H | rs374712231 |
-2.46 | 0.997 | N | 0.595 | 0.573 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 1E-03 | None | None | None | 0 | None |
| R/H | rs374712231 |
-2.46 | 0.997 | N | 0.595 | 0.573 | None | gnomAD-4.0.0 | 4.93351E-05 | None | None | None | None | N | None | 1.25874E-04 | 0 | None | 0 | 9.20217E-05 | None | 0 | 0 | 5.14811E-05 | 2.89243E-05 | 1.73557E-05 |
| R/L | rs374712231 |
-1.027 | 0.954 | N | 0.643 | 0.532 | None | gnomAD-2.1.1 | 9.93E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2E-05 | 0 |
| R/L | rs374712231 |
-1.027 | 0.954 | N | 0.643 | 0.532 | None | gnomAD-4.0.0 | 1.48394E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.8892E-06 | 0 | 0 |
| R/S | None | None | 0.954 | N | 0.621 | 0.485 | 0.473065174198 | gnomAD-4.0.0 | 2.22258E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.83116E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9805 | likely_pathogenic | 0.9864 | pathogenic | -2.113 | Highly Destabilizing | 0.916 | D | 0.515 | neutral | None | None | None | None | N |
| R/C | 0.6731 | likely_pathogenic | 0.7551 | pathogenic | -1.909 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.474005812 | None | None | N |
| R/D | 0.9981 | likely_pathogenic | 0.9985 | pathogenic | -0.83 | Destabilizing | 0.975 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/E | 0.9721 | likely_pathogenic | 0.9767 | pathogenic | -0.615 | Destabilizing | 0.845 | D | 0.449 | neutral | None | None | None | None | N |
| R/F | 0.9924 | likely_pathogenic | 0.9955 | pathogenic | -1.338 | Destabilizing | 0.996 | D | 0.824 | deleterious | None | None | None | None | N |
| R/G | 0.9642 | likely_pathogenic | 0.9747 | pathogenic | -2.459 | Highly Destabilizing | 0.954 | D | 0.643 | neutral | N | 0.504035803 | None | None | N |
| R/H | 0.7766 | likely_pathogenic | 0.8493 | pathogenic | -2.189 | Highly Destabilizing | 0.997 | D | 0.595 | neutral | N | 0.521494949 | None | None | N |
| R/I | 0.9766 | likely_pathogenic | 0.9847 | pathogenic | -1.104 | Destabilizing | 0.987 | D | 0.835 | deleterious | None | None | None | None | N |
| R/K | 0.5111 | ambiguous | 0.635 | pathogenic | -1.311 | Destabilizing | 0.693 | D | 0.477 | neutral | None | None | None | None | N |
| R/L | 0.9414 | likely_pathogenic | 0.9611 | pathogenic | -1.104 | Destabilizing | 0.954 | D | 0.643 | neutral | N | 0.498173227 | None | None | N |
| R/M | 0.9407 | likely_pathogenic | 0.9646 | pathogenic | -1.54 | Destabilizing | 0.997 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/N | 0.9931 | likely_pathogenic | 0.995 | pathogenic | -1.225 | Destabilizing | 0.975 | D | 0.569 | neutral | None | None | None | None | N |
| R/P | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -1.43 | Destabilizing | 0.993 | D | 0.781 | deleterious | D | 0.536218615 | None | None | N |
| R/Q | 0.5749 | likely_pathogenic | 0.6551 | pathogenic | -1.165 | Destabilizing | 0.253 | N | 0.335 | neutral | None | None | None | None | N |
| R/S | 0.9936 | likely_pathogenic | 0.9955 | pathogenic | -2.222 | Highly Destabilizing | 0.954 | D | 0.621 | neutral | N | 0.486839693 | None | None | N |
| R/T | 0.9809 | likely_pathogenic | 0.9902 | pathogenic | -1.792 | Destabilizing | 0.975 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/V | 0.9744 | likely_pathogenic | 0.9827 | pathogenic | -1.43 | Destabilizing | 0.975 | D | 0.798 | deleterious | None | None | None | None | N |
| R/W | 0.9157 | likely_pathogenic | 0.9419 | pathogenic | -0.772 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| R/Y | 0.971 | likely_pathogenic | 0.9794 | pathogenic | -0.663 | Destabilizing | 0.996 | D | 0.803 | deleterious | 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.