Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20483 | 61672;61673;61674 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| N2AB | 18842 | 56749;56750;56751 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| N2A | 17915 | 53968;53969;53970 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| N2B | 11418 | 34477;34478;34479 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| Novex-1 | 11543 | 34852;34853;34854 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| Novex-2 | 11610 | 35053;35054;35055 | chr2:178590278;178590277;178590276 | chr2:179455005;179455004;179455003 |
| 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 | rs770139489  |
-0.407 | 1.0 | N | 0.679 | 0.348 | 0.509053020717 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.46E-05 | 0 |
| R/C | rs770139489 |
-0.407 | 1.0 | N | 0.679 | 0.348 | 0.509053020717 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/C | rs770139489 |
-0.407 | 1.0 | N | 0.679 | 0.348 | 0.509053020717 | gnomAD-4.0.0 | 6.99394E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.48305E-06 | 0 | 0 |
| R/H | rs748693257 |
-0.904 | 0.641 | N | 0.306 | 0.19 | 0.110078149338 | gnomAD-2.1.1 | 9.29E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.77E-05 | None | 0 | None | 0 | 1E-05 | 0 |
| R/H | rs748693257 |
-0.904 | 0.641 | N | 0.306 | 0.19 | 0.110078149338 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs748693257 |
-0.904 | 0.641 | N | 0.306 | 0.19 | 0.110078149338 | gnomAD-4.0.0 | 2.41634E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.74673E-05 | None | 0 | 0 | 2.67258E-05 | 2.42324E-05 | 3.29685E-05 |
| R/L | rs748693257 |
None | 0.999 | N | 0.539 | 0.405 | 0.383256108077 | gnomAD-4.0.0 | 7.03911E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.15771E-07 | 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 | 0.8162 | likely_pathogenic | 0.7577 | pathogenic | -0.028 | Destabilizing | 0.992 | D | 0.57 | neutral | None | None | None | None | N |
| R/C | 0.5403 | ambiguous | 0.4544 | ambiguous | -0.021 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.455892697 | None | None | N |
| R/D | 0.9317 | likely_pathogenic | 0.917 | pathogenic | -0.073 | Destabilizing | 0.998 | D | 0.599 | neutral | None | None | None | None | N |
| R/E | 0.752 | likely_pathogenic | 0.7078 | pathogenic | -0.018 | Destabilizing | 0.983 | D | 0.575 | neutral | None | None | None | None | N |
| R/F | 0.9254 | likely_pathogenic | 0.8976 | pathogenic | -0.278 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| R/G | 0.6386 | likely_pathogenic | 0.5718 | pathogenic | -0.22 | Destabilizing | 0.996 | D | 0.528 | neutral | N | 0.493609282 | None | None | N |
| R/H | 0.2673 | likely_benign | 0.2157 | benign | -0.748 | Destabilizing | 0.641 | D | 0.306 | neutral | N | 0.461632936 | None | None | N |
| R/I | 0.7906 | likely_pathogenic | 0.738 | pathogenic | 0.44 | Stabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| R/K | 0.1706 | likely_benign | 0.158 | benign | -0.024 | Destabilizing | 0.96 | D | 0.579 | neutral | None | None | None | None | N |
| R/L | 0.6744 | likely_pathogenic | 0.5916 | pathogenic | 0.44 | Stabilizing | 0.999 | D | 0.539 | neutral | N | 0.430096521 | None | None | N |
| R/M | 0.7428 | likely_pathogenic | 0.6669 | pathogenic | 0.128 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| R/N | 0.8725 | likely_pathogenic | 0.8559 | pathogenic | 0.306 | Stabilizing | 0.983 | D | 0.558 | neutral | None | None | None | None | N |
| R/P | 0.9188 | likely_pathogenic | 0.908 | pathogenic | 0.304 | Stabilizing | 1.0 | D | 0.625 | neutral | N | 0.433888975 | None | None | N |
| R/Q | 0.2171 | likely_benign | 0.1822 | benign | 0.154 | Stabilizing | 0.998 | D | 0.577 | neutral | None | None | None | None | N |
| R/S | 0.8473 | likely_pathogenic | 0.8068 | pathogenic | -0.069 | Destabilizing | 0.996 | D | 0.563 | neutral | N | 0.447412845 | None | None | N |
| R/T | 0.6933 | likely_pathogenic | 0.6046 | pathogenic | 0.114 | Stabilizing | 0.998 | D | 0.543 | neutral | None | None | None | None | N |
| R/V | 0.8148 | likely_pathogenic | 0.7676 | pathogenic | 0.304 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| R/W | 0.5504 | ambiguous | 0.4343 | ambiguous | -0.321 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8278 | likely_pathogenic | 0.7766 | pathogenic | 0.09 | Stabilizing | 0.995 | D | 0.635 | 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.