Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23351 | 70276;70277;70278 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| N2AB | 21710 | 65353;65354;65355 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| N2A | 20783 | 62572;62573;62574 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| N2B | 14286 | 43081;43082;43083 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| Novex-1 | 14411 | 43456;43457;43458 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| Novex-2 | 14478 | 43657;43658;43659 | chr2:178576081;178576080;178576079 | chr2:179440808;179440807;179440806 |
| 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/L | rs376046188  |
0.471 | 0.565 | D | 0.565 | 0.248 | 0.490419987736 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/L | rs376046188 |
0.471 | 0.565 | D | 0.565 | 0.248 | 0.490419987736 | gnomAD-4.0.0 | 1.36864E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79917E-06 | 0 | 0 |
| R/P | None | None | 0.949 | N | 0.575 | 0.332 | 0.412980791724 | gnomAD-4.0.0 | 6.84318E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99586E-07 | 0 | 0 |
| R/Q | rs376046188 |
0.13 | 0.04 | D | 0.379 | 0.125 | 0.191931220699 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.79236E-04 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/Q | rs376046188 |
0.13 | 0.04 | D | 0.379 | 0.125 | 0.191931220699 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 1.93648E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs376046188 |
0.13 | 0.04 | D | 0.379 | 0.125 | 0.191931220699 | gnomAD-4.0.0 | 8.6772E-06 | None | None | None | None | I | None | 0 | 4.99967E-05 | None | 0 | 1.33947E-04 | None | 3.1252E-05 | 0 | 8.47754E-07 | 2.19645E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9381 | likely_pathogenic | 0.9351 | pathogenic | -0.22 | Destabilizing | 0.004 | N | 0.397 | neutral | None | None | None | None | I |
| R/C | 0.683 | likely_pathogenic | 0.6049 | pathogenic | -0.168 | Destabilizing | 0.973 | D | 0.605 | neutral | None | None | None | None | I |
| R/D | 0.9887 | likely_pathogenic | 0.9878 | pathogenic | 0.061 | Stabilizing | 0.826 | D | 0.508 | neutral | None | None | None | None | I |
| R/E | 0.9193 | likely_pathogenic | 0.9125 | pathogenic | 0.168 | Stabilizing | 0.404 | N | 0.6 | neutral | None | None | None | None | I |
| R/F | 0.9659 | likely_pathogenic | 0.9571 | pathogenic | -0.194 | Destabilizing | 0.906 | D | 0.591 | neutral | None | None | None | None | I |
| R/G | 0.856 | likely_pathogenic | 0.8354 | pathogenic | -0.5 | Destabilizing | 0.565 | D | 0.565 | neutral | N | 0.516953941 | None | None | I |
| R/H | 0.5098 | ambiguous | 0.4417 | ambiguous | -1.013 | Destabilizing | 0.826 | D | 0.577 | neutral | None | None | None | None | I |
| R/I | 0.9202 | likely_pathogenic | 0.9084 | pathogenic | 0.509 | Stabilizing | 0.826 | D | 0.597 | neutral | None | None | None | None | I |
| R/K | 0.3614 | ambiguous | 0.3266 | benign | -0.217 | Destabilizing | 0.218 | N | 0.599 | neutral | None | None | None | None | I |
| R/L | 0.7905 | likely_pathogenic | 0.7597 | pathogenic | 0.509 | Stabilizing | 0.565 | D | 0.565 | neutral | D | 0.530152525 | None | None | I |
| R/M | 0.8925 | likely_pathogenic | 0.8757 | pathogenic | 0.076 | Stabilizing | 0.973 | D | 0.56 | neutral | None | None | None | None | I |
| R/N | 0.9717 | likely_pathogenic | 0.9703 | pathogenic | 0.161 | Stabilizing | 0.826 | D | 0.542 | neutral | None | None | None | None | I |
| R/P | 0.9772 | likely_pathogenic | 0.9787 | pathogenic | 0.288 | Stabilizing | 0.949 | D | 0.575 | neutral | N | 0.515241788 | None | None | I |
| R/Q | 0.3801 | ambiguous | 0.3345 | benign | 0.063 | Stabilizing | 0.04 | N | 0.379 | neutral | D | 0.532440682 | None | None | I |
| R/S | 0.9612 | likely_pathogenic | 0.9561 | pathogenic | -0.365 | Destabilizing | 0.404 | N | 0.584 | neutral | None | None | None | None | I |
| R/T | 0.9249 | likely_pathogenic | 0.9202 | pathogenic | -0.088 | Destabilizing | 0.575 | D | 0.575 | neutral | None | None | None | None | I |
| R/V | 0.9364 | likely_pathogenic | 0.9281 | pathogenic | 0.288 | Stabilizing | 0.704 | D | 0.527 | neutral | None | None | None | None | I |
| R/W | 0.6798 | likely_pathogenic | 0.6229 | pathogenic | -0.072 | Destabilizing | 0.991 | D | 0.632 | neutral | None | None | None | None | I |
| R/Y | 0.9092 | likely_pathogenic | 0.8903 | pathogenic | 0.289 | Stabilizing | 0.906 | D | 0.578 | 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.