Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19479 | 58660;58661;58662 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| N2AB | 17838 | 53737;53738;53739 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| N2A | 16911 | 50956;50957;50958 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| N2B | 10414 | 31465;31466;31467 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| Novex-1 | 10539 | 31840;31841;31842 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| Novex-2 | 10606 | 32041;32042;32043 | chr2:178593865;178593864;178593863 | chr2:179458592;179458591;179458590 |
| 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 | rs768666860  |
-0.549 | 1.0 | N | 0.857 | 0.389 | 0.575712373409 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.54E-05 | None | 0 | 0 | 0 |
| R/C | rs768666860 |
-0.549 | 1.0 | N | 0.857 | 0.389 | 0.575712373409 | gnomAD-4.0.0 | 6.86725E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.95652E-04 | 2.70152E-06 | 3.5529E-05 | 0 |
| R/H | rs2288569 |
-1.161 | 1.0 | N | 0.784 | 0.463 | None | gnomAD-2.1.1 | 1.74251E-01 | None | None | None | None | I | None | 7.19275E-02 | 1.49893E-01 | None | 1.73444E-01 | 4.31415E-01 | None | 2.65477E-01 | None | 1.51649E-01 | 1.457E-01 | 1.62504E-01 |
| R/H | rs2288569 |
-1.161 | 1.0 | N | 0.784 | 0.463 | None | gnomAD-3.1.2 | 1.42208E-01 | None | None | None | None | I | None | 7.56783E-02 | 1.29391E-01 | 4.72527E-01 | 1.74754E-01 | 4.40946E-01 | None | 1.6331E-01 | 1.13924E-01 | 1.45641E-01 | 2.63213E-01 | 1.28955E-01 |
| R/H | rs2288569 |
-1.161 | 1.0 | N | 0.784 | 0.463 | None | 1000 genomes | 2.1246E-01 | None | None | None | None | I | None | 6.66E-02 | 1.513E-01 | None | None | 4.544E-01 | 1.402E-01 | None | None | None | 2.781E-01 | None |
| R/H | rs2288569 |
-1.161 | 1.0 | N | 0.784 | 0.463 | None | gnomAD-4.0.0 | 1.53386E-01 | None | None | None | None | I | None | 7.40343E-02 | 1.43709E-01 | None | 1.7421E-01 | 4.30079E-01 | None | 1.53113E-01 | 1.31779E-01 | 1.39271E-01 | 2.58419E-01 | 1.62847E-01 |
| R/L | rs2288569 |
0.035 | 1.0 | N | 0.682 | 0.377 | None | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.04E-06 | 0 |
| R/L | rs2288569 |
0.035 | 1.0 | N | 0.682 | 0.377 | None | gnomAD-4.0.0 | 1.37171E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80037E-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 | 0.6929 | likely_pathogenic | 0.6668 | pathogenic | -0.454 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | I |
| R/C | 0.2446 | likely_benign | 0.2107 | benign | -0.337 | Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.479747851 | None | None | I |
| R/D | 0.9511 | likely_pathogenic | 0.9458 | pathogenic | -0.124 | Destabilizing | 0.999 | D | 0.827 | deleterious | None | None | None | None | I |
| R/E | 0.7146 | likely_pathogenic | 0.6956 | pathogenic | -0.063 | Destabilizing | 0.998 | D | 0.675 | prob.neutral | None | None | None | None | I |
| R/F | 0.8231 | likely_pathogenic | 0.7889 | pathogenic | -0.659 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| R/G | 0.6908 | likely_pathogenic | 0.6639 | pathogenic | -0.673 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.490597178 | None | None | I |
| R/H | 0.2331 | likely_benign | 0.2259 | benign | -1.068 | Destabilizing | 1.0 | D | 0.784 | deleterious | N | 0.479494362 | None | None | I |
| R/I | 0.3834 | ambiguous | 0.3523 | ambiguous | 0.101 | Stabilizing | 0.999 | D | 0.83 | deleterious | None | None | None | None | I |
| R/K | 0.1503 | likely_benign | 0.1455 | benign | -0.429 | Destabilizing | 0.995 | D | 0.543 | neutral | None | None | None | None | I |
| R/L | 0.4755 | ambiguous | 0.4383 | ambiguous | 0.101 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.500420611 | None | None | I |
| R/M | 0.5148 | ambiguous | 0.4781 | ambiguous | -0.041 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| R/N | 0.8743 | likely_pathogenic | 0.8574 | pathogenic | 0.108 | Stabilizing | 0.999 | D | 0.774 | deleterious | None | None | None | None | I |
| R/P | 0.773 | likely_pathogenic | 0.7741 | pathogenic | -0.064 | Destabilizing | 1.0 | D | 0.813 | deleterious | N | 0.482986856 | None | None | I |
| R/Q | 0.19 | likely_benign | 0.1742 | benign | -0.166 | Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | I |
| R/S | 0.8012 | likely_pathogenic | 0.779 | pathogenic | -0.495 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.463592153 | None | None | I |
| R/T | 0.5079 | ambiguous | 0.4754 | ambiguous | -0.294 | Destabilizing | 0.999 | D | 0.744 | deleterious | None | None | None | None | I |
| R/V | 0.4943 | ambiguous | 0.4652 | ambiguous | -0.064 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | I |
| R/W | 0.4595 | ambiguous | 0.4019 | ambiguous | -0.512 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| R/Y | 0.7052 | likely_pathogenic | 0.6455 | pathogenic | -0.144 | Destabilizing | 0.999 | D | 0.87 | deleterious | 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.