Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22197 | 66814;66815;66816 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| N2AB | 20556 | 61891;61892;61893 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| N2A | 19629 | 59110;59111;59112 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| N2B | 13132 | 39619;39620;39621 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| Novex-1 | 13257 | 39994;39995;39996 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| Novex-2 | 13324 | 40195;40196;40197 | chr2:178581679;178581678;178581677 | chr2:179446406;179446405;179446404 |
| 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/Q | rs374656017  |
-0.195 | 0.999 | N | 0.557 | 0.211 | None | gnomAD-2.1.1 | 9.69E-05 | None | None | None | None | N | None | 3.73134E-04 | 0 | None | 0 | 6.78355E-04 | None | 3.28E-05 | None | 0 | 1.57E-05 | 2.83126E-04 |
| R/Q | rs374656017 |
-0.195 | 0.999 | N | 0.557 | 0.211 | None | gnomAD-3.1.2 | 1.57882E-04 | None | None | None | None | N | None | 3.86287E-04 | 0 | 0 | 0 | 7.75795E-04 | None | 0 | 0 | 1.47E-05 | 2.079E-04 | 9.5511E-04 |
| R/Q | rs374656017 |
-0.195 | 0.999 | N | 0.557 | 0.211 | None | gnomAD-4.0.0 | 6.38772E-05 | None | None | None | None | N | None | 2.80142E-04 | 0 | None | 0 | 6.50603E-04 | None | 0 | 0 | 2.54415E-05 | 6.59558E-05 | 2.72357E-04 |
| R/W | rs774696610 |
-0.581 | 1.0 | N | 0.723 | 0.282 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 2.07366E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| R/W | rs774696610 |
-0.581 | 1.0 | N | 0.723 | 0.282 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 1.69049E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs774696610 |
-0.581 | 1.0 | N | 0.723 | 0.282 | None | gnomAD-4.0.0 | 1.05438E-05 | None | None | None | None | N | None | 1.20276E-04 | 0 | None | 0 | 2.24215E-05 | None | 0 | 0 | 3.3923E-06 | 0 | 4.80769E-05 |
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 | 0.5313 | ambiguous | 0.5363 | ambiguous | -0.731 | Destabilizing | 0.916 | D | 0.527 | neutral | None | None | None | None | N |
| R/C | 0.3204 | likely_benign | 0.3253 | benign | -0.6 | Destabilizing | 0.999 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/D | 0.7685 | likely_pathogenic | 0.7636 | pathogenic | -0.016 | Destabilizing | 0.996 | D | 0.68 | prob.neutral | None | None | None | None | N |
| R/E | 0.4756 | ambiguous | 0.4688 | ambiguous | 0.123 | Stabilizing | 0.957 | D | 0.55 | neutral | None | None | None | None | N |
| R/F | 0.7988 | likely_pathogenic | 0.8073 | pathogenic | -0.525 | Destabilizing | 0.975 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/G | 0.4683 | ambiguous | 0.4805 | ambiguous | -1.053 | Destabilizing | 0.993 | D | 0.519 | neutral | N | 0.498508961 | None | None | N |
| R/H | 0.195 | likely_benign | 0.2005 | benign | -1.51 | Destabilizing | 0.999 | D | 0.572 | neutral | None | None | None | None | N |
| R/I | 0.4617 | ambiguous | 0.4659 | ambiguous | 0.138 | Stabilizing | 0.95 | D | 0.577 | neutral | None | None | None | None | N |
| R/K | 0.1272 | likely_benign | 0.1256 | benign | -0.646 | Destabilizing | 0.901 | D | 0.489 | neutral | None | None | None | None | N |
| R/L | 0.3239 | likely_benign | 0.3371 | benign | 0.138 | Stabilizing | 0.062 | N | 0.37 | neutral | N | 0.48719589 | None | None | N |
| R/M | 0.3749 | ambiguous | 0.3846 | ambiguous | -0.251 | Destabilizing | 0.975 | D | 0.644 | neutral | None | None | None | None | N |
| R/N | 0.6983 | likely_pathogenic | 0.6936 | pathogenic | -0.201 | Destabilizing | 0.996 | D | 0.547 | neutral | None | None | None | None | N |
| R/P | 0.497 | ambiguous | 0.4973 | ambiguous | -0.13 | Destabilizing | 0.998 | D | 0.675 | neutral | N | 0.479285695 | None | None | N |
| R/Q | 0.1496 | likely_benign | 0.1461 | benign | -0.298 | Destabilizing | 0.999 | D | 0.557 | neutral | N | 0.483134077 | None | None | N |
| R/S | 0.7049 | likely_pathogenic | 0.6976 | pathogenic | -0.916 | Destabilizing | 0.987 | D | 0.571 | neutral | None | None | None | None | N |
| R/T | 0.4042 | ambiguous | 0.4109 | ambiguous | -0.584 | Destabilizing | 0.916 | D | 0.575 | neutral | None | None | None | None | N |
| R/V | 0.5118 | ambiguous | 0.5112 | ambiguous | -0.13 | Destabilizing | 0.845 | D | 0.569 | neutral | None | None | None | None | N |
| R/W | 0.4251 | ambiguous | 0.4353 | ambiguous | -0.227 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.474091036 | None | None | N |
| R/Y | 0.6283 | likely_pathogenic | 0.6319 | pathogenic | 0.063 | Stabilizing | 0.987 | D | 0.687 | prob.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.