Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21809 | 65650;65651;65652 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| N2AB | 20168 | 60727;60728;60729 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| N2A | 19241 | 57946;57947;57948 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| N2B | 12744 | 38455;38456;38457 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| Novex-1 | 12869 | 38830;38831;38832 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| Novex-2 | 12936 | 39031;39032;39033 | chr2:178583757;178583756;178583755 | chr2:179448484;179448483;179448482 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs756088419  |
0.141 | 0.782 | N | 0.403 | 0.32 | 0.357724736475 | gnomAD-2.1.1 | 8.14E-06 | None | None | None | None | I | None | 0 | 2.92E-05 | None | 0 | 5.7E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs756088419 |
0.141 | 0.782 | N | 0.403 | 0.32 | 0.357724736475 | gnomAD-4.0.0 | 1.37023E-06 | None | None | None | None | I | None | 0 | 2.24336E-05 | None | 0 | 2.53768E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | None | 0.642 | N | 0.411 | 0.231 | 0.296329037015 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | None | None | 0.642 | N | 0.411 | 0.231 | 0.296329037015 | gnomAD-4.0.0 | 1.86144E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54471E-06 | 0 | 0 |
| T/S | rs756088419 |
-0.144 | 0.003 | N | 0.119 | 0.076 | 0.144782658237 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.7E-05 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs756088419 |
-0.144 | 0.003 | N | 0.119 | 0.076 | 0.144782658237 | gnomAD-4.0.0 | 1.37023E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.53768E-05 | None | 0 | 0 | 9.00142E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.066 | likely_benign | 0.0626 | benign | -0.25 | Destabilizing | 0.006 | N | 0.13 | neutral | N | 0.512552907 | None | None | I |
| T/C | 0.411 | ambiguous | 0.3543 | ambiguous | -0.196 | Destabilizing | 0.973 | D | 0.447 | neutral | None | None | None | None | I |
| T/D | 0.3394 | likely_benign | 0.3358 | benign | 0.154 | Stabilizing | 0.826 | D | 0.414 | neutral | None | None | None | None | I |
| T/E | 0.293 | likely_benign | 0.2934 | benign | 0.081 | Stabilizing | 0.404 | N | 0.427 | neutral | None | None | None | None | I |
| T/F | 0.2612 | likely_benign | 0.2226 | benign | -0.753 | Destabilizing | 0.906 | D | 0.553 | neutral | None | None | None | None | I |
| T/G | 0.1775 | likely_benign | 0.1692 | benign | -0.372 | Destabilizing | 0.404 | N | 0.473 | neutral | None | None | None | None | I |
| T/H | 0.2284 | likely_benign | 0.2125 | benign | -0.532 | Destabilizing | 0.973 | D | 0.553 | neutral | None | None | None | None | I |
| T/I | 0.1569 | likely_benign | 0.1402 | benign | -0.047 | Destabilizing | 0.782 | D | 0.403 | neutral | N | 0.516073215 | None | None | I |
| T/K | 0.2185 | likely_benign | 0.2204 | benign | -0.267 | Destabilizing | 0.404 | N | 0.417 | neutral | None | None | None | None | I |
| T/L | 0.0911 | likely_benign | 0.0855 | benign | -0.047 | Destabilizing | 0.575 | D | 0.451 | neutral | None | None | None | None | I |
| T/M | 0.0976 | likely_benign | 0.0885 | benign | -0.045 | Destabilizing | 0.991 | D | 0.439 | neutral | None | None | None | None | I |
| T/N | 0.1032 | likely_benign | 0.1007 | benign | 0.009 | Stabilizing | 0.642 | D | 0.411 | neutral | N | 0.511707545 | None | None | I |
| T/P | 0.0822 | likely_benign | 0.0791 | benign | -0.087 | Destabilizing | 0.879 | D | 0.433 | neutral | N | 0.51867359 | None | None | I |
| T/Q | 0.2141 | likely_benign | 0.2124 | benign | -0.202 | Destabilizing | 0.826 | D | 0.43 | neutral | None | None | None | None | I |
| T/R | 0.199 | likely_benign | 0.2 | benign | 0.045 | Stabilizing | 0.826 | D | 0.434 | neutral | None | None | None | None | I |
| T/S | 0.0872 | likely_benign | 0.0829 | benign | -0.196 | Destabilizing | 0.003 | N | 0.119 | neutral | N | 0.47488274 | None | None | I |
| T/V | 0.1142 | likely_benign | 0.1066 | benign | -0.087 | Destabilizing | 0.575 | D | 0.438 | neutral | None | None | None | None | I |
| T/W | 0.5686 | likely_pathogenic | 0.5393 | ambiguous | -0.802 | Destabilizing | 0.991 | D | 0.652 | neutral | None | None | None | None | I |
| T/Y | 0.2667 | likely_benign | 0.2409 | benign | -0.501 | Destabilizing | 0.967 | D | 0.553 | 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.