Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24088 | 72487;72488;72489 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| N2AB | 22447 | 67564;67565;67566 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| N2A | 21520 | 64783;64784;64785 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| N2B | 15023 | 45292;45293;45294 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| Novex-1 | 15148 | 45667;45668;45669 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| Novex-2 | 15215 | 45868;45869;45870 | chr2:178573870;178573869;178573868 | chr2:179438597;179438596;179438595 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs774226045  |
-2.817 | 0.027 | N | 0.627 | 0.181 | 0.351180957027 | gnomAD-2.1.1 | 1.16869E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.51568E-04 | None | 0 | 0 | 0 |
| V/A | rs774226045 |
-2.817 | 0.027 | N | 0.627 | 0.181 | 0.351180957027 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| V/A | rs774226045 |
-2.817 | 0.027 | N | 0.627 | 0.181 | 0.351180957027 | gnomAD-4.0.0 | 4.4693E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 7.80632E-04 | 1.60467E-05 |
| V/E | None | None | 0.317 | N | 0.646 | 0.218 | 0.618265897142 | gnomAD-4.0.0 | 2.05633E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70305E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1502 | likely_benign | 0.1687 | benign | -2.075 | Highly Destabilizing | 0.027 | N | 0.627 | neutral | N | 0.492124791 | None | None | N |
| V/C | 0.5296 | ambiguous | 0.5541 | ambiguous | -1.55 | Destabilizing | 0.935 | D | 0.624 | neutral | None | None | None | None | N |
| V/D | 0.2962 | likely_benign | 0.3324 | benign | -2.634 | Highly Destabilizing | 0.38 | N | 0.683 | prob.neutral | None | None | None | None | N |
| V/E | 0.2169 | likely_benign | 0.2284 | benign | -2.467 | Highly Destabilizing | 0.317 | N | 0.646 | neutral | N | 0.513817635 | None | None | N |
| V/F | 0.1115 | likely_benign | 0.122 | benign | -1.234 | Destabilizing | 0.38 | N | 0.66 | neutral | None | None | None | None | N |
| V/G | 0.197 | likely_benign | 0.2257 | benign | -2.548 | Highly Destabilizing | 0.317 | N | 0.691 | prob.neutral | N | 0.500140188 | None | None | N |
| V/H | 0.364 | ambiguous | 0.3732 | ambiguous | -2.229 | Highly Destabilizing | 0.935 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/I | 0.0618 | likely_benign | 0.0611 | benign | -0.772 | Destabilizing | None | N | 0.164 | neutral | N | 0.44495777 | None | None | N |
| V/K | 0.3017 | likely_benign | 0.3033 | benign | -1.685 | Destabilizing | 0.38 | N | 0.644 | neutral | None | None | None | None | N |
| V/L | 0.1042 | likely_benign | 0.1106 | benign | -0.772 | Destabilizing | 0.004 | N | 0.485 | neutral | N | 0.482918725 | None | None | N |
| V/M | 0.1049 | likely_benign | 0.1142 | benign | -0.799 | Destabilizing | 0.38 | N | 0.644 | neutral | None | None | None | None | N |
| V/N | 0.1964 | likely_benign | 0.2186 | benign | -1.87 | Destabilizing | 0.38 | N | 0.698 | prob.neutral | None | None | None | None | N |
| V/P | 0.8856 | likely_pathogenic | 0.9145 | pathogenic | -1.179 | Destabilizing | 0.555 | D | 0.658 | neutral | None | None | None | None | N |
| V/Q | 0.2286 | likely_benign | 0.2318 | benign | -1.804 | Destabilizing | 0.555 | D | 0.634 | neutral | None | None | None | None | N |
| V/R | 0.2436 | likely_benign | 0.2464 | benign | -1.402 | Destabilizing | 0.38 | N | 0.701 | prob.neutral | None | None | None | None | N |
| V/S | 0.1494 | likely_benign | 0.1624 | benign | -2.446 | Highly Destabilizing | 0.081 | N | 0.655 | neutral | None | None | None | None | N |
| V/T | 0.1244 | likely_benign | 0.136 | benign | -2.158 | Highly Destabilizing | 0.001 | N | 0.227 | neutral | None | None | None | None | N |
| V/W | 0.5636 | ambiguous | 0.6043 | pathogenic | -1.716 | Destabilizing | 0.935 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/Y | 0.3328 | likely_benign | 0.3463 | ambiguous | -1.378 | Destabilizing | 0.555 | D | 0.669 | 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.