Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3088 | 9487;9488;9489 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| N2AB | 3088 | 9487;9488;9489 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| N2A | 3088 | 9487;9488;9489 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| N2B | 3042 | 9349;9350;9351 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| Novex-1 | 3042 | 9349;9350;9351 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| Novex-2 | 3042 | 9349;9350;9351 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
| Novex-3 | 3088 | 9487;9488;9489 | chr2:178768057;178768056;178768055 | chr2:179632784;179632783;179632782 |
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/E | None | None | 0.942 | D | 0.785 | 0.834 | 0.86188130804 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| V/I | rs776977480  |
-0.487 | 0.656 | D | 0.565 | 0.327 | 0.613412721671 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.30659E-04 | None | 0 | 0 | 0 |
| V/I | rs776977480 |
-0.487 | 0.656 | D | 0.565 | 0.327 | 0.613412721671 | gnomAD-4.0.0 | 8.893E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99292E-07 | 1.04338E-04 | 4.96738E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7484 | likely_pathogenic | 0.7245 | pathogenic | -1.766 | Destabilizing | 0.014 | N | 0.335 | neutral | D | 0.662297084 | None | None | N |
| V/C | 0.9457 | likely_pathogenic | 0.9455 | pathogenic | -1.048 | Destabilizing | 0.994 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/D | 0.9973 | likely_pathogenic | 0.9956 | pathogenic | -2.215 | Highly Destabilizing | 0.978 | D | 0.786 | deleterious | None | None | None | None | N |
| V/E | 0.9914 | likely_pathogenic | 0.9857 | pathogenic | -2.093 | Highly Destabilizing | 0.942 | D | 0.785 | deleterious | D | 0.798081116 | None | None | N |
| V/F | 0.8168 | likely_pathogenic | 0.7382 | pathogenic | -1.167 | Destabilizing | 0.978 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/G | 0.9301 | likely_pathogenic | 0.9091 | pathogenic | -2.179 | Highly Destabilizing | 0.89 | D | 0.765 | deleterious | D | 0.609441404 | None | None | N |
| V/H | 0.9971 | likely_pathogenic | 0.9949 | pathogenic | -1.779 | Destabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | N |
| V/I | 0.1311 | likely_benign | 0.1413 | benign | -0.662 | Destabilizing | 0.656 | D | 0.565 | neutral | D | 0.525026073 | None | None | N |
| V/K | 0.9944 | likely_pathogenic | 0.9913 | pathogenic | -1.553 | Destabilizing | 0.956 | D | 0.784 | deleterious | None | None | None | None | N |
| V/L | 0.6908 | likely_pathogenic | 0.6556 | pathogenic | -0.662 | Destabilizing | 0.489 | N | 0.606 | neutral | D | 0.590221428 | None | None | N |
| V/M | 0.643 | likely_pathogenic | 0.5954 | pathogenic | -0.506 | Destabilizing | 0.993 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/N | 0.991 | likely_pathogenic | 0.9869 | pathogenic | -1.567 | Destabilizing | 0.978 | D | 0.792 | deleterious | None | None | None | None | N |
| V/P | 0.9599 | likely_pathogenic | 0.9537 | pathogenic | -1.001 | Destabilizing | 0.978 | D | 0.781 | deleterious | None | None | None | None | N |
| V/Q | 0.9897 | likely_pathogenic | 0.9831 | pathogenic | -1.597 | Destabilizing | 0.978 | D | 0.788 | deleterious | None | None | None | None | N |
| V/R | 0.9902 | likely_pathogenic | 0.9845 | pathogenic | -1.168 | Destabilizing | 0.956 | D | 0.784 | deleterious | None | None | None | None | N |
| V/S | 0.9346 | likely_pathogenic | 0.916 | pathogenic | -2.054 | Highly Destabilizing | 0.915 | D | 0.763 | deleterious | None | None | None | None | N |
| V/T | 0.79 | likely_pathogenic | 0.7531 | pathogenic | -1.815 | Destabilizing | 0.86 | D | 0.629 | neutral | None | None | None | None | N |
| V/W | 0.9973 | likely_pathogenic | 0.9955 | pathogenic | -1.545 | Destabilizing | 0.998 | D | 0.773 | deleterious | None | None | None | None | N |
| V/Y | 0.9883 | likely_pathogenic | 0.9812 | pathogenic | -1.184 | Destabilizing | 0.993 | D | 0.728 | 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.