Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29530 | 88813;88814;88815 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| N2AB | 27889 | 83890;83891;83892 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| N2A | 26962 | 81109;81110;81111 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| N2B | 20465 | 61618;61619;61620 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| Novex-1 | 20590 | 61993;61994;61995 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| Novex-2 | 20657 | 62194;62195;62196 | chr2:178554871;178554870;178554869 | chr2:179419598;179419597;179419596 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs780772770  |
None | 0.64 | D | 0.587 | 0.286 | 0.465294738428 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs780772770 |
None | 0.64 | D | 0.587 | 0.286 | 0.465294738428 | gnomAD-4.0.0 | 6.57151E-06 | None | None | None | None | I | None | 2.41313E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs794729524 |
-0.087 | 0.995 | D | 0.715 | 0.638 | 0.885704332653 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.29618E-04 | 0 |
| I/N | rs794729524 |
-0.087 | 0.995 | D | 0.715 | 0.638 | 0.885704332653 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/N | rs794729524 |
-0.087 | 0.995 | D | 0.715 | 0.638 | 0.885704332653 | gnomAD-4.0.0 | 1.48722E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.86468E-05 | 0 | 3.20236E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9794 | likely_pathogenic | 0.9793 | pathogenic | -2.502 | Highly Destabilizing | 0.825 | D | 0.648 | neutral | None | None | None | None | I |
| I/C | 0.9701 | likely_pathogenic | 0.9702 | pathogenic | -2.258 | Highly Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/D | 0.9985 | likely_pathogenic | 0.9989 | pathogenic | -3.129 | Highly Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | I |
| I/E | 0.9973 | likely_pathogenic | 0.9976 | pathogenic | -2.998 | Highly Destabilizing | 0.988 | D | 0.703 | prob.neutral | None | None | None | None | I |
| I/F | 0.7183 | likely_pathogenic | 0.7145 | pathogenic | -1.619 | Destabilizing | 0.968 | D | 0.632 | neutral | D | 0.536817499 | None | None | I |
| I/G | 0.9961 | likely_pathogenic | 0.9961 | pathogenic | -2.927 | Highly Destabilizing | 0.988 | D | 0.697 | prob.neutral | None | None | None | None | I |
| I/H | 0.9948 | likely_pathogenic | 0.995 | pathogenic | -2.147 | Highly Destabilizing | 0.999 | D | 0.72 | prob.delet. | None | None | None | None | I |
| I/K | 0.9933 | likely_pathogenic | 0.9943 | pathogenic | -1.901 | Destabilizing | 0.988 | D | 0.699 | prob.neutral | None | None | None | None | I |
| I/L | 0.4825 | ambiguous | 0.4616 | ambiguous | -1.309 | Destabilizing | 0.211 | N | 0.521 | neutral | N | 0.505454442 | None | None | I |
| I/M | 0.5168 | ambiguous | 0.5154 | ambiguous | -1.477 | Destabilizing | 0.64 | D | 0.587 | neutral | D | 0.536990858 | None | None | I |
| I/N | 0.9691 | likely_pathogenic | 0.9721 | pathogenic | -2.138 | Highly Destabilizing | 0.995 | D | 0.715 | prob.delet. | D | 0.537337574 | None | None | I |
| I/P | 0.9925 | likely_pathogenic | 0.9923 | pathogenic | -1.686 | Destabilizing | 0.996 | D | 0.707 | prob.neutral | None | None | None | None | I |
| I/Q | 0.9949 | likely_pathogenic | 0.9955 | pathogenic | -2.199 | Highly Destabilizing | 0.988 | D | 0.713 | prob.delet. | None | None | None | None | I |
| I/R | 0.9912 | likely_pathogenic | 0.9922 | pathogenic | -1.402 | Destabilizing | 0.988 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/S | 0.9804 | likely_pathogenic | 0.9818 | pathogenic | -2.747 | Highly Destabilizing | 0.984 | D | 0.663 | neutral | N | 0.518309096 | None | None | I |
| I/T | 0.973 | likely_pathogenic | 0.9738 | pathogenic | -2.492 | Highly Destabilizing | 0.896 | D | 0.691 | prob.neutral | N | 0.499549977 | None | None | I |
| I/V | 0.1577 | likely_benign | 0.1555 | benign | -1.686 | Destabilizing | 0.046 | N | 0.395 | neutral | N | 0.356346203 | None | None | I |
| I/W | 0.9957 | likely_pathogenic | 0.996 | pathogenic | -1.865 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | I |
| I/Y | 0.9685 | likely_pathogenic | 0.9697 | pathogenic | -1.635 | Destabilizing | 0.988 | D | 0.695 | prob.neutral | 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.