Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22326 | 67201;67202;67203 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| N2AB | 20685 | 62278;62279;62280 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| N2A | 19758 | 59497;59498;59499 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| N2B | 13261 | 40006;40007;40008 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| Novex-1 | 13386 | 40381;40382;40383 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| Novex-2 | 13453 | 40582;40583;40584 | chr2:178580403;178580402;178580401 | chr2:179445130;179445129;179445128 |
| 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/Q | None | None | 0.822 | N | 0.425 | 0.142 | 0.126345400529 | gnomAD-4.0.0 | 1.59239E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86043E-06 | 0 | 0 |
| K/R | rs202125813  |
0.149 | 0.006 | N | 0.223 | 0.055 | None | gnomAD-2.1.1 | 4.93463E-04 | None | None | None | None | I | None | 5.24967E-03 | 2.54626E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 1.40607E-04 |
| K/R | rs202125813 |
0.149 | 0.006 | N | 0.223 | 0.055 | None | gnomAD-3.1.2 | 1.63049E-03 | None | None | None | None | I | None | 5.66784E-03 | 7.20555E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| K/R | rs202125813 |
0.149 | 0.006 | N | 0.223 | 0.055 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | I | None | 3.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| K/R | rs202125813 |
0.149 | 0.006 | N | 0.223 | 0.055 | None | gnomAD-4.0.0 | 3.01865E-04 | None | None | None | None | I | None | 5.73165E-03 | 4.33348E-04 | None | 0 | 0 | None | 0 | 1.6518E-04 | 9.32627E-06 | 0 | 3.04253E-04 |
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 | 0.8973 | likely_pathogenic | 0.9262 | pathogenic | -0.205 | Destabilizing | 0.86 | D | 0.46 | neutral | None | None | None | None | I |
| K/C | 0.9085 | likely_pathogenic | 0.9245 | pathogenic | -0.256 | Destabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | I |
| K/D | 0.988 | likely_pathogenic | 0.9924 | pathogenic | 0.01 | Stabilizing | 0.978 | D | 0.389 | neutral | None | None | None | None | I |
| K/E | 0.8374 | likely_pathogenic | 0.882 | pathogenic | 0.06 | Stabilizing | 0.822 | D | 0.43 | neutral | N | 0.43898815 | None | None | I |
| K/F | 0.9873 | likely_pathogenic | 0.9907 | pathogenic | -0.215 | Destabilizing | 0.993 | D | 0.559 | neutral | None | None | None | None | I |
| K/G | 0.9398 | likely_pathogenic | 0.958 | pathogenic | -0.462 | Destabilizing | 0.86 | D | 0.457 | neutral | None | None | None | None | I |
| K/H | 0.7276 | likely_pathogenic | 0.7465 | pathogenic | -0.722 | Destabilizing | 0.978 | D | 0.453 | neutral | None | None | None | None | I |
| K/I | 0.8452 | likely_pathogenic | 0.8904 | pathogenic | 0.415 | Stabilizing | 0.97 | D | 0.555 | neutral | N | 0.487723459 | None | None | I |
| K/L | 0.8593 | likely_pathogenic | 0.8956 | pathogenic | 0.415 | Stabilizing | 0.86 | D | 0.457 | neutral | None | None | None | None | I |
| K/M | 0.8018 | likely_pathogenic | 0.858 | pathogenic | 0.084 | Stabilizing | 0.998 | D | 0.462 | neutral | None | None | None | None | I |
| K/N | 0.957 | likely_pathogenic | 0.9723 | pathogenic | 0.027 | Stabilizing | 0.822 | D | 0.406 | neutral | N | 0.480778844 | None | None | I |
| K/P | 0.9675 | likely_pathogenic | 0.9748 | pathogenic | 0.237 | Stabilizing | 0.993 | D | 0.446 | neutral | None | None | None | None | I |
| K/Q | 0.5198 | ambiguous | 0.6005 | pathogenic | -0.05 | Destabilizing | 0.822 | D | 0.425 | neutral | N | 0.474332875 | None | None | I |
| K/R | 0.0717 | likely_benign | 0.0739 | benign | -0.223 | Destabilizing | 0.006 | N | 0.223 | neutral | N | 0.330377818 | None | None | I |
| K/S | 0.9398 | likely_pathogenic | 0.9583 | pathogenic | -0.453 | Destabilizing | 0.86 | D | 0.427 | neutral | None | None | None | None | I |
| K/T | 0.805 | likely_pathogenic | 0.8708 | pathogenic | -0.233 | Destabilizing | 0.822 | D | 0.426 | neutral | N | 0.455131038 | None | None | I |
| K/V | 0.8395 | likely_pathogenic | 0.8759 | pathogenic | 0.237 | Stabilizing | 0.978 | D | 0.459 | neutral | None | None | None | None | I |
| K/W | 0.979 | likely_pathogenic | 0.9836 | pathogenic | -0.226 | Destabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | I |
| K/Y | 0.9383 | likely_pathogenic | 0.9503 | pathogenic | 0.09 | Stabilizing | 0.993 | D | 0.525 | 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.