Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22651 | 68176;68177;68178 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| N2AB | 21010 | 63253;63254;63255 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| N2A | 20083 | 60472;60473;60474 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| N2B | 13586 | 40981;40982;40983 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| Novex-1 | 13711 | 41356;41357;41358 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| Novex-2 | 13778 | 41557;41558;41559 | chr2:178579079;178579078;178579077 | chr2:179443806;179443805;179443804 |
| 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/V | rs544473873  |
-1.488 | 0.005 | N | 0.181 | 0.092 | 0.237489013734 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 0 |
| I/V | rs544473873 |
-1.488 | 0.005 | N | 0.181 | 0.092 | 0.237489013734 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs544473873 |
-1.488 | 0.005 | N | 0.181 | 0.092 | 0.237489013734 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs544473873 |
-1.488 | 0.005 | N | 0.181 | 0.092 | 0.237489013734 | gnomAD-4.0.0 | 5.07482E-06 | None | None | None | None | N | None | 1.74423E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.82011E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8928 | likely_pathogenic | 0.8792 | pathogenic | -2.178 | Highly Destabilizing | 0.525 | D | 0.649 | neutral | None | None | None | None | N |
| I/C | 0.9139 | likely_pathogenic | 0.9094 | pathogenic | -1.366 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | None | None | None | None | N |
| I/D | 0.9969 | likely_pathogenic | 0.9966 | pathogenic | -2.486 | Highly Destabilizing | 0.991 | D | 0.785 | deleterious | None | None | None | None | N |
| I/E | 0.9909 | likely_pathogenic | 0.9896 | pathogenic | -2.212 | Highly Destabilizing | 0.974 | D | 0.777 | deleterious | None | None | None | None | N |
| I/F | 0.4193 | ambiguous | 0.4357 | ambiguous | -1.151 | Destabilizing | 0.012 | N | 0.453 | neutral | N | 0.494007219 | None | None | N |
| I/G | 0.9844 | likely_pathogenic | 0.982 | pathogenic | -2.764 | Highly Destabilizing | 0.915 | D | 0.766 | deleterious | None | None | None | None | N |
| I/H | 0.9897 | likely_pathogenic | 0.9888 | pathogenic | -2.412 | Highly Destabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | N |
| I/K | 0.987 | likely_pathogenic | 0.9854 | pathogenic | -1.592 | Destabilizing | 0.949 | D | 0.777 | deleterious | None | None | None | None | N |
| I/L | 0.1548 | likely_benign | 0.1563 | benign | -0.472 | Destabilizing | 0.111 | N | 0.475 | neutral | N | 0.435353199 | None | None | N |
| I/M | 0.2173 | likely_benign | 0.1952 | benign | -0.509 | Destabilizing | 0.267 | N | 0.514 | neutral | N | 0.467027145 | None | None | N |
| I/N | 0.9686 | likely_pathogenic | 0.9666 | pathogenic | -2.04 | Highly Destabilizing | 0.989 | D | 0.794 | deleterious | N | 0.494539149 | None | None | N |
| I/P | 0.9448 | likely_pathogenic | 0.9427 | pathogenic | -1.023 | Destabilizing | 0.991 | D | 0.795 | deleterious | None | None | None | None | N |
| I/Q | 0.982 | likely_pathogenic | 0.98 | pathogenic | -1.78 | Destabilizing | 0.974 | D | 0.799 | deleterious | None | None | None | None | N |
| I/R | 0.9793 | likely_pathogenic | 0.9775 | pathogenic | -1.582 | Destabilizing | 0.974 | D | 0.797 | deleterious | None | None | None | None | N |
| I/S | 0.9534 | likely_pathogenic | 0.9495 | pathogenic | -2.71 | Highly Destabilizing | 0.891 | D | 0.738 | prob.delet. | N | 0.494285659 | None | None | N |
| I/T | 0.9211 | likely_pathogenic | 0.9153 | pathogenic | -2.278 | Highly Destabilizing | 0.801 | D | 0.707 | prob.neutral | N | 0.475927915 | None | None | N |
| I/V | 0.0864 | likely_benign | 0.0734 | benign | -1.023 | Destabilizing | 0.005 | N | 0.181 | neutral | N | 0.417389088 | None | None | N |
| I/W | 0.9779 | likely_pathogenic | 0.98 | pathogenic | -1.604 | Destabilizing | 0.998 | D | 0.777 | deleterious | None | None | None | None | N |
| I/Y | 0.9385 | likely_pathogenic | 0.9408 | pathogenic | -1.251 | Destabilizing | 0.904 | D | 0.758 | deleterious | 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.