Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28796 | 86611;86612;86613 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| N2AB | 27155 | 81688;81689;81690 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| N2A | 26228 | 78907;78908;78909 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| N2B | 19731 | 59416;59417;59418 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| Novex-1 | 19856 | 59791;59792;59793 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| Novex-2 | 19923 | 59992;59993;59994 | chr2:178559746;178559745;178559744 | chr2:179424473;179424472;179424471 |
| 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 | rs778069260  |
-0.203 | 0.992 | N | 0.611 | 0.514 | 0.681924071509 | gnomAD-2.1.1 | 2.62E-05 | None | None | None | None | N | None | 4.15E-05 | 5.83E-05 | None | 0 | 0 | None | 0 | None | 1.27421E-04 | 8.12E-06 | 0 |
| R/C | rs778069260 |
-0.203 | 0.992 | N | 0.611 | 0.514 | 0.681924071509 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.92604E-04 | None | 3.77074E-04 | 0 | 0 | 0 | 0 |
| R/C | rs778069260 |
-0.203 | 0.992 | N | 0.611 | 0.514 | 0.681924071509 | gnomAD-4.0.0 | 2.18909E-05 | None | None | None | None | N | None | 4.02037E-05 | 3.38535E-05 | None | 0 | 2.23524E-05 | None | 2.06894E-04 | 0 | 1.36518E-05 | 0 | 0 |
| R/G | None | None | 0.264 | N | 0.573 | 0.262 | 0.475192790171 | gnomAD-4.0.0 | 6.9123E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0581E-07 | 0 | 0 |
| R/H | rs181167673 |
-0.795 | 0.011 | D | 0.319 | 0.182 | None | gnomAD-2.1.1 | 1.27E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.79E-05 | 0 |
| R/H | rs181167673 |
-0.795 | 0.011 | D | 0.319 | 0.182 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92827E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs181167673 |
-0.795 | 0.011 | D | 0.319 | 0.182 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/H | rs181167673 |
-0.795 | 0.011 | D | 0.319 | 0.182 | None | gnomAD-4.0.0 | 7.50582E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23584E-05 | None | 0 | 0 | 9.38599E-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 | 0.3143 | likely_benign | 0.2906 | benign | -0.015 | Destabilizing | 0.072 | N | 0.556 | neutral | None | None | None | None | N |
| R/C | 0.14 | likely_benign | 0.1273 | benign | -0.195 | Destabilizing | 0.992 | D | 0.611 | neutral | N | 0.495900681 | None | None | N |
| R/D | 0.5337 | ambiguous | 0.4954 | ambiguous | -0.226 | Destabilizing | 0.567 | D | 0.521 | neutral | None | None | None | None | N |
| R/E | 0.3062 | likely_benign | 0.3022 | benign | -0.19 | Destabilizing | 0.157 | N | 0.548 | neutral | None | None | None | None | N |
| R/F | 0.4712 | ambiguous | 0.4221 | ambiguous | -0.345 | Destabilizing | 0.567 | D | 0.613 | neutral | None | None | None | None | N |
| R/G | 0.1768 | likely_benign | 0.1663 | benign | -0.156 | Destabilizing | 0.264 | N | 0.573 | neutral | N | 0.445517917 | None | None | N |
| R/H | 0.0872 | likely_benign | 0.0785 | benign | -0.628 | Destabilizing | 0.011 | N | 0.319 | neutral | D | 0.53629185 | None | None | N |
| R/I | 0.2995 | likely_benign | 0.28 | benign | 0.311 | Stabilizing | 0.726 | D | 0.612 | neutral | None | None | None | None | N |
| R/K | 0.1058 | likely_benign | 0.1044 | benign | -0.128 | Destabilizing | 0.133 | N | 0.515 | neutral | None | None | None | None | N |
| R/L | 0.2134 | likely_benign | 0.1869 | benign | 0.311 | Stabilizing | 0.417 | N | 0.552 | neutral | D | 0.525517496 | None | None | N |
| R/M | 0.2758 | likely_benign | 0.2734 | benign | -0.027 | Destabilizing | 0.968 | D | 0.565 | neutral | None | None | None | None | N |
| R/N | 0.413 | ambiguous | 0.371 | ambiguous | 0.043 | Stabilizing | 0.157 | N | 0.537 | neutral | None | None | None | None | N |
| R/P | 0.4867 | ambiguous | 0.4316 | ambiguous | 0.221 | Stabilizing | 0.836 | D | 0.597 | neutral | N | 0.459889937 | None | None | N |
| R/Q | 0.0874 | likely_benign | 0.0856 | benign | -0.046 | Destabilizing | 0.567 | D | 0.531 | neutral | None | None | None | None | N |
| R/S | 0.3504 | ambiguous | 0.3234 | benign | -0.212 | Destabilizing | 0.01 | N | 0.345 | neutral | N | 0.450248947 | None | None | N |
| R/T | 0.2242 | likely_benign | 0.2088 | benign | -0.067 | Destabilizing | 0.157 | N | 0.584 | neutral | None | None | None | None | N |
| R/V | 0.3534 | ambiguous | 0.3216 | benign | 0.221 | Stabilizing | 0.567 | D | 0.568 | neutral | None | None | None | None | N |
| R/W | 0.1795 | likely_benign | 0.1744 | benign | -0.49 | Destabilizing | 0.968 | D | 0.629 | neutral | None | None | None | None | N |
| R/Y | 0.3041 | likely_benign | 0.2624 | benign | -0.081 | Destabilizing | 0.396 | N | 0.599 | 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.