Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29936 | 90031;90032;90033 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| N2AB | 28295 | 85108;85109;85110 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| N2A | 27368 | 82327;82328;82329 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| N2B | 20871 | 62836;62837;62838 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| Novex-1 | 20996 | 63211;63212;63213 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| Novex-2 | 21063 | 63412;63413;63414 | chr2:178553094;178553093;178553092 | chr2:179417821;179417820;179417819 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | None | None | 0.565 | N | 0.749 | 0.443 | 0.53837629882 | gnomAD-4.0.0 | 1.59813E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77917E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs188667007  |
-1.269 | 0.008 | N | 0.323 | 0.206 | 0.27855597813 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/T | rs188667007 |
-1.269 | 0.008 | N | 0.323 | 0.206 | 0.27855597813 | gnomAD-4.0.0 | 4.79461E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.62203E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4837 | ambiguous | 0.4688 | ambiguous | -0.838 | Destabilizing | 0.996 | D | 0.681 | prob.neutral | None | None | None | None | N |
| A/D | 0.4493 | ambiguous | 0.4382 | ambiguous | -2.192 | Highly Destabilizing | 0.565 | D | 0.749 | deleterious | N | 0.514983581 | None | None | N |
| A/E | 0.3132 | likely_benign | 0.3032 | benign | -2.286 | Highly Destabilizing | 0.024 | N | 0.473 | neutral | None | None | None | None | N |
| A/F | 0.4639 | ambiguous | 0.423 | ambiguous | -1.301 | Destabilizing | 0.961 | D | 0.777 | deleterious | None | None | None | None | N |
| A/G | 0.1727 | likely_benign | 0.1661 | benign | -0.976 | Destabilizing | 0.722 | D | 0.592 | neutral | N | 0.513716133 | None | None | N |
| A/H | 0.5503 | ambiguous | 0.5177 | ambiguous | -1.07 | Destabilizing | 0.989 | D | 0.763 | deleterious | None | None | None | None | N |
| A/I | 0.3034 | likely_benign | 0.2805 | benign | -0.557 | Destabilizing | 0.858 | D | 0.761 | deleterious | None | None | None | None | N |
| A/K | 0.4633 | ambiguous | 0.4381 | ambiguous | -1.106 | Destabilizing | 0.633 | D | 0.734 | prob.delet. | None | None | None | None | N |
| A/L | 0.2559 | likely_benign | 0.2383 | benign | -0.557 | Destabilizing | 0.633 | D | 0.725 | prob.delet. | None | None | None | None | N |
| A/M | 0.3195 | likely_benign | 0.2872 | benign | -0.264 | Destabilizing | 0.989 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/N | 0.3412 | ambiguous | 0.3156 | benign | -0.904 | Destabilizing | 0.923 | D | 0.763 | deleterious | None | None | None | None | N |
| A/P | 0.1178 | likely_benign | 0.1242 | benign | -0.612 | Destabilizing | 0.018 | N | 0.473 | neutral | N | 0.379524133 | None | None | N |
| A/Q | 0.3303 | likely_benign | 0.3137 | benign | -1.249 | Destabilizing | 0.858 | D | 0.782 | deleterious | None | None | None | None | N |
| A/R | 0.4072 | ambiguous | 0.376 | ambiguous | -0.602 | Destabilizing | 0.923 | D | 0.765 | deleterious | None | None | None | None | N |
| A/S | 0.1064 | likely_benign | 0.105 | benign | -0.985 | Destabilizing | 0.565 | D | 0.581 | neutral | N | 0.481115247 | None | None | N |
| A/T | 0.128 | likely_benign | 0.1217 | benign | -1.03 | Destabilizing | 0.008 | N | 0.323 | neutral | N | 0.495865368 | None | None | N |
| A/V | 0.1654 | likely_benign | 0.1526 | benign | -0.612 | Destabilizing | 0.565 | D | 0.599 | neutral | N | 0.486711108 | None | None | N |
| A/W | 0.8244 | likely_pathogenic | 0.8044 | pathogenic | -1.559 | Destabilizing | 0.996 | D | 0.796 | deleterious | None | None | None | None | N |
| A/Y | 0.5641 | likely_pathogenic | 0.5282 | ambiguous | -1.199 | Destabilizing | 0.987 | D | 0.771 | 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.