Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24861 | 74806;74807;74808 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| N2AB | 23220 | 69883;69884;69885 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| N2A | 22293 | 67102;67103;67104 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| N2B | 15796 | 47611;47612;47613 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| Novex-1 | 15921 | 47986;47987;47988 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| Novex-2 | 15988 | 48187;48188;48189 | chr2:178571551;178571550;178571549 | chr2:179436278;179436277;179436276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs879142245  |
-0.15 | 0.999 | N | 0.771 | 0.383 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/P | rs879142245 |
-0.15 | 0.999 | N | 0.771 | 0.383 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | rs879142245 |
-0.15 | 0.999 | N | 0.771 | 0.383 | None | gnomAD-4.0.0 | 7.43891E-06 | None | None | None | None | I | None | 1.33533E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32529E-06 | 0 | 0 |
| A/V | rs149232991 |
-0.042 | 0.998 | N | 0.665 | 0.268 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | I | None | 3.23457E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs149232991 |
-0.042 | 0.998 | N | 0.665 | 0.268 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 1.93209E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs149232991 |
-0.042 | 0.998 | N | 0.665 | 0.268 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/V | rs149232991 |
-0.042 | 0.998 | N | 0.665 | 0.268 | None | gnomAD-4.0.0 | 1.23975E-05 | None | None | None | None | I | None | 2.66745E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7621 | likely_pathogenic | 0.736 | pathogenic | -0.922 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| A/D | 0.8806 | likely_pathogenic | 0.8826 | pathogenic | -0.728 | Destabilizing | 0.999 | D | 0.775 | deleterious | N | 0.468303485 | None | None | I |
| A/E | 0.8146 | likely_pathogenic | 0.7883 | pathogenic | -0.834 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| A/F | 0.8527 | likely_pathogenic | 0.8286 | pathogenic | -1.046 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| A/G | 0.3039 | likely_benign | 0.3151 | benign | -0.835 | Destabilizing | 0.996 | D | 0.5 | neutral | N | 0.466303329 | None | None | I |
| A/H | 0.8967 | likely_pathogenic | 0.8883 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| A/I | 0.7982 | likely_pathogenic | 0.7637 | pathogenic | -0.452 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| A/K | 0.9153 | likely_pathogenic | 0.8989 | pathogenic | -0.961 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| A/L | 0.5535 | ambiguous | 0.5177 | ambiguous | -0.452 | Destabilizing | 0.998 | D | 0.697 | prob.neutral | None | None | None | None | I |
| A/M | 0.6155 | likely_pathogenic | 0.5738 | pathogenic | -0.372 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | I |
| A/N | 0.6599 | likely_pathogenic | 0.6612 | pathogenic | -0.655 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | I |
| A/P | 0.7068 | likely_pathogenic | 0.7069 | pathogenic | -0.49 | Destabilizing | 0.999 | D | 0.771 | deleterious | N | 0.504456286 | None | None | I |
| A/Q | 0.7333 | likely_pathogenic | 0.6916 | pathogenic | -0.909 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| A/R | 0.8737 | likely_pathogenic | 0.8484 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| A/S | 0.1432 | likely_benign | 0.1534 | benign | -0.969 | Destabilizing | 0.957 | D | 0.299 | neutral | N | 0.424301991 | None | None | I |
| A/T | 0.2574 | likely_benign | 0.2406 | benign | -0.986 | Destabilizing | 0.992 | D | 0.636 | neutral | N | 0.45098716 | None | None | I |
| A/V | 0.5105 | ambiguous | 0.4623 | ambiguous | -0.49 | Destabilizing | 0.998 | D | 0.665 | neutral | N | 0.481765853 | None | None | I |
| A/W | 0.9736 | likely_pathogenic | 0.968 | pathogenic | -1.233 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| A/Y | 0.894 | likely_pathogenic | 0.8811 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.79 | deleterious | 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.