Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28283 | 85072;85073;85074 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| N2AB | 26642 | 80149;80150;80151 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| N2A | 25715 | 77368;77369;77370 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| N2B | 19218 | 57877;57878;57879 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| Novex-1 | 19343 | 58252;58253;58254 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| Novex-2 | 19410 | 58453;58454;58455 | chr2:178561285;178561284;178561283 | chr2:179426012;179426011;179426010 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | None | None | 0.864 | N | 0.611 | 0.221 | 0.183819452728 | gnomAD-4.0.0 | 1.59124E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-06 | 0 | 0 |
| K/R | rs545841306  |
0.225 | 0.013 | N | 0.343 | 0.095 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs545841306 |
0.225 | 0.013 | N | 0.343 | 0.095 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 1.68862E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs545841306 |
0.225 | 0.013 | N | 0.343 | 0.095 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| K/R | rs545841306 |
0.225 | 0.013 | N | 0.343 | 0.095 | None | gnomAD-4.0.0 | 8.11853E-06 | None | None | None | None | I | None | 1.39465E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4111 | ambiguous | 0.3776 | ambiguous | -0.024 | Destabilizing | 0.707 | D | 0.651 | neutral | None | None | None | None | I |
| K/C | 0.7399 | likely_pathogenic | 0.7406 | pathogenic | -0.11 | Destabilizing | 0.995 | D | 0.729 | prob.delet. | None | None | None | None | I |
| K/D | 0.785 | likely_pathogenic | 0.755 | pathogenic | -0.021 | Destabilizing | 0.894 | D | 0.649 | neutral | None | None | None | None | I |
| K/E | 0.3636 | ambiguous | 0.3107 | benign | -0.012 | Destabilizing | 0.477 | N | 0.605 | neutral | N | 0.492196278 | None | None | I |
| K/F | 0.8543 | likely_pathogenic | 0.8267 | pathogenic | -0.196 | Destabilizing | 0.945 | D | 0.733 | prob.delet. | None | None | None | None | I |
| K/G | 0.6065 | likely_pathogenic | 0.5982 | pathogenic | -0.241 | Destabilizing | 0.894 | D | 0.586 | neutral | None | None | None | None | I |
| K/H | 0.4188 | ambiguous | 0.4003 | ambiguous | -0.552 | Destabilizing | 0.985 | D | 0.629 | neutral | None | None | None | None | I |
| K/I | 0.445 | ambiguous | 0.4015 | ambiguous | 0.472 | Stabilizing | 0.809 | D | 0.729 | prob.delet. | None | None | None | None | I |
| K/L | 0.4575 | ambiguous | 0.4192 | ambiguous | 0.472 | Stabilizing | 0.547 | D | 0.623 | neutral | None | None | None | None | I |
| K/M | 0.3288 | likely_benign | 0.304 | benign | 0.311 | Stabilizing | 0.273 | N | 0.587 | neutral | N | 0.471003617 | None | None | I |
| K/N | 0.6372 | likely_pathogenic | 0.6032 | pathogenic | 0.222 | Stabilizing | 0.864 | D | 0.611 | neutral | N | 0.46776116 | None | None | I |
| K/P | 0.5541 | ambiguous | 0.5252 | ambiguous | 0.335 | Stabilizing | 0.945 | D | 0.664 | neutral | None | None | None | None | I |
| K/Q | 0.195 | likely_benign | 0.1796 | benign | 0.04 | Stabilizing | 0.864 | D | 0.627 | neutral | N | 0.475318804 | None | None | I |
| K/R | 0.0803 | likely_benign | 0.08 | benign | -0.065 | Destabilizing | 0.013 | N | 0.343 | neutral | N | 0.477904403 | None | None | I |
| K/S | 0.5785 | likely_pathogenic | 0.5496 | ambiguous | -0.252 | Destabilizing | 0.707 | D | 0.617 | neutral | None | None | None | None | I |
| K/T | 0.3213 | likely_benign | 0.2909 | benign | -0.092 | Destabilizing | 0.864 | D | 0.601 | neutral | N | 0.50316542 | None | None | I |
| K/V | 0.3412 | ambiguous | 0.3205 | benign | 0.335 | Stabilizing | 0.547 | D | 0.596 | neutral | None | None | None | None | I |
| K/W | 0.8262 | likely_pathogenic | 0.8145 | pathogenic | -0.205 | Destabilizing | 0.995 | D | 0.753 | deleterious | None | None | None | None | I |
| K/Y | 0.7465 | likely_pathogenic | 0.7217 | pathogenic | 0.14 | Stabilizing | 0.945 | D | 0.713 | prob.delet. | 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.