Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31315 | 94168;94169;94170 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| N2AB | 29674 | 89245;89246;89247 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| N2A | 28747 | 86464;86465;86466 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| N2B | 22250 | 66973;66974;66975 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| Novex-1 | 22375 | 67348;67349;67350 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| Novex-2 | 22442 | 67549;67550;67551 | chr2:178547683;178547682;178547681 | chr2:179412410;179412409;179412408 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | None | None | 1.0 | D | 0.729 | 0.452 | 0.745503425957 | gnomAD-4.0.0 | 1.59103E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| P/S | rs1160417169  |
-0.548 | 0.957 | N | 0.35 | 0.42 | 0.376745185316 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs1160417169 |
-0.548 | 0.957 | N | 0.35 | 0.42 | 0.376745185316 | gnomAD-4.0.0 | 3.18211E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1789 | likely_benign | 0.21 | benign | -0.385 | Destabilizing | 0.992 | D | 0.592 | neutral | D | 0.523644088 | None | None | N |
| P/C | 0.6238 | likely_pathogenic | 0.6781 | pathogenic | -0.757 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| P/D | 0.4787 | ambiguous | 0.4806 | ambiguous | -0.141 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/E | 0.3677 | ambiguous | 0.3933 | ambiguous | -0.246 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| P/F | 0.7004 | likely_pathogenic | 0.7488 | pathogenic | -0.588 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/G | 0.4829 | ambiguous | 0.489 | ambiguous | -0.497 | Destabilizing | 0.997 | D | 0.668 | neutral | None | None | None | None | N |
| P/H | 0.3248 | likely_benign | 0.3524 | ambiguous | -0.01 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.524911535 | None | None | N |
| P/I | 0.5078 | ambiguous | 0.559 | ambiguous | -0.234 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| P/K | 0.376 | ambiguous | 0.4026 | ambiguous | -0.39 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| P/L | 0.2608 | likely_benign | 0.314 | benign | -0.234 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | N | 0.499709574 | None | None | N |
| P/M | 0.4759 | ambiguous | 0.5128 | ambiguous | -0.475 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/N | 0.4096 | ambiguous | 0.4155 | ambiguous | -0.201 | Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| P/Q | 0.2736 | likely_benign | 0.3117 | benign | -0.401 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| P/R | 0.2933 | likely_benign | 0.3377 | benign | 0.077 | Stabilizing | 0.999 | D | 0.759 | deleterious | N | 0.506300301 | None | None | N |
| P/S | 0.2513 | likely_benign | 0.2859 | benign | -0.571 | Destabilizing | 0.957 | D | 0.35 | neutral | N | 0.501438456 | None | None | N |
| P/T | 0.1987 | likely_benign | 0.2178 | benign | -0.572 | Destabilizing | 0.998 | D | 0.72 | prob.delet. | N | 0.47494041 | None | None | N |
| P/V | 0.3651 | ambiguous | 0.4156 | ambiguous | -0.252 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| P/W | 0.8468 | likely_pathogenic | 0.8777 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| P/Y | 0.6578 | likely_pathogenic | 0.698 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | 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.