Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33674 | 101245;101246;101247 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| N2AB | 32033 | 96322;96323;96324 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| N2A | 31106 | 93541;93542;93543 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| N2B | 24609 | 74050;74051;74052 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| Novex-1 | 24734 | 74425;74426;74427 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| Novex-2 | 24801 | 74626;74627;74628 | chr2:178535595;178535594;178535593 | chr2:179400322;179400321;179400320 |
| 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/K | rs766217871  |
0.082 | 0.953 | N | 0.481 | 0.313 | 0.303453137403 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs766217871 |
0.082 | 0.953 | N | 0.481 | 0.313 | 0.303453137403 | gnomAD-4.0.0 | 1.59123E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| R/T | rs766217871 |
0.037 | 0.999 | N | 0.621 | 0.469 | 0.653912592101 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs766217871 |
0.037 | 0.999 | N | 0.621 | 0.469 | 0.653912592101 | gnomAD-4.0.0 | 1.59123E-06 | None | None | None | None | I | None | 5.65867E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.9698 | likely_pathogenic | 0.9282 | pathogenic | -0.002 | Destabilizing | 0.998 | D | 0.558 | neutral | None | None | None | None | I |
| R/C | 0.8935 | likely_pathogenic | 0.7685 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| R/D | 0.9842 | likely_pathogenic | 0.9617 | pathogenic | -0.276 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/E | 0.9585 | likely_pathogenic | 0.907 | pathogenic | -0.195 | Destabilizing | 0.994 | D | 0.618 | neutral | None | None | None | None | I |
| R/F | 0.9925 | likely_pathogenic | 0.979 | pathogenic | -0.24 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/G | 0.9538 | likely_pathogenic | 0.8875 | pathogenic | -0.196 | Destabilizing | 0.999 | D | 0.584 | neutral | N | 0.454540045 | None | None | I |
| R/H | 0.7282 | likely_pathogenic | 0.5413 | ambiguous | -0.889 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/I | 0.941 | likely_pathogenic | 0.8634 | pathogenic | 0.476 | Stabilizing | 0.998 | D | 0.725 | prob.delet. | N | 0.499504331 | None | None | I |
| R/K | 0.619 | likely_pathogenic | 0.4813 | ambiguous | -0.159 | Destabilizing | 0.953 | D | 0.481 | neutral | N | 0.456750844 | None | None | I |
| R/L | 0.9285 | likely_pathogenic | 0.8357 | pathogenic | 0.476 | Stabilizing | 0.999 | D | 0.584 | neutral | None | None | None | None | I |
| R/M | 0.9736 | likely_pathogenic | 0.9313 | pathogenic | -0.106 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/N | 0.9778 | likely_pathogenic | 0.9457 | pathogenic | -0.134 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/P | 0.9553 | likely_pathogenic | 0.8973 | pathogenic | 0.337 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| R/Q | 0.7135 | likely_pathogenic | 0.5327 | ambiguous | -0.118 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/S | 0.9737 | likely_pathogenic | 0.9365 | pathogenic | -0.344 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.443626832 | None | None | I |
| R/T | 0.9641 | likely_pathogenic | 0.9056 | pathogenic | -0.125 | Destabilizing | 0.999 | D | 0.621 | neutral | N | 0.494501156 | None | None | I |
| R/V | 0.9618 | likely_pathogenic | 0.9151 | pathogenic | 0.337 | Stabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/W | 0.9399 | likely_pathogenic | 0.8664 | pathogenic | -0.384 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | I |
| R/Y | 0.9713 | likely_pathogenic | 0.9305 | pathogenic | 0.036 | Stabilizing | 0.999 | D | 0.718 | prob.delet. | 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.