Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34175 | 102748;102749;102750 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| N2AB | 32534 | 97825;97826;97827 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| N2A | 31607 | 95044;95045;95046 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| N2B | 25110 | 75553;75554;75555 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| Novex-1 | 25235 | 75928;75929;75930 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| Novex-2 | 25302 | 76129;76130;76131 | chr2:178534092;178534091;178534090 | chr2:179398819;179398818;179398817 |
| 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 | rs201954720  |
0.111 | 1.0 | N | 0.685 | 0.336 | None | gnomAD-2.1.1 | 5.35E-05 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 4E-05 | 8.59E-05 | 0 |
| R/Q | rs201954720 |
0.111 | 1.0 | N | 0.685 | 0.336 | None | gnomAD-3.1.2 | 1.1172E-04 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.76398E-04 | 4.14594E-04 | 0 |
| R/Q | rs201954720 |
0.111 | 1.0 | N | 0.685 | 0.336 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| R/Q | rs201954720 |
0.111 | 1.0 | N | 0.685 | 0.336 | None | gnomAD-4.0.0 | 7.93104E-05 | None | None | None | None | I | None | 7.99574E-05 | 0 | None | 0 | 1.55985E-04 | None | 3.12422E-05 | 0 | 8.47577E-05 | 1.31761E-04 | 1.60036E-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 | 0.8203 | likely_pathogenic | 0.8523 | pathogenic | -0.629 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | I |
| R/C | 0.468 | ambiguous | 0.5711 | pathogenic | -0.821 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/D | 0.9017 | likely_pathogenic | 0.9167 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| R/E | 0.6334 | likely_pathogenic | 0.6883 | pathogenic | 0.034 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| R/F | 0.869 | likely_pathogenic | 0.8995 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/G | 0.7032 | likely_pathogenic | 0.7446 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.602 | neutral | N | 0.500947126 | None | None | I |
| R/H | 0.2092 | likely_benign | 0.2335 | benign | -1.198 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| R/I | 0.6662 | likely_pathogenic | 0.7413 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | I |
| R/K | 0.2215 | likely_benign | 0.2288 | benign | -0.451 | Destabilizing | 0.998 | D | 0.573 | neutral | None | None | None | None | I |
| R/L | 0.5847 | likely_pathogenic | 0.6379 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.602 | neutral | D | 0.534443624 | None | None | I |
| R/M | 0.6781 | likely_pathogenic | 0.7431 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| R/N | 0.8247 | likely_pathogenic | 0.8588 | pathogenic | -0.451 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/P | 0.97 | likely_pathogenic | 0.9739 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | D | 0.524015986 | None | None | I |
| R/Q | 0.189 | likely_benign | 0.2071 | benign | -0.427 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.468717277 | None | None | I |
| R/S | 0.8099 | likely_pathogenic | 0.8445 | pathogenic | -1.049 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| R/T | 0.6099 | likely_pathogenic | 0.6688 | pathogenic | -0.708 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| R/V | 0.7461 | likely_pathogenic | 0.8031 | pathogenic | -0.093 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | I |
| R/W | 0.4767 | ambiguous | 0.5262 | ambiguous | -0.283 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/Y | 0.7104 | likely_pathogenic | 0.7667 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.691 | 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.