Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15023 | 45292;45293;45294 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| N2AB | 13382 | 40369;40370;40371 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| N2A | 12455 | 37588;37589;37590 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| N2B | 5958 | 18097;18098;18099 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| Novex-1 | 6083 | 18472;18473;18474 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| Novex-2 | 6150 | 18673;18674;18675 | chr2:178621855;178621854;178621853 | chr2:179486582;179486581;179486580 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs373308815  |
-0.769 | 0.454 | N | 0.522 | 0.101 | 0.308904156042 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12841E-04 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs373308815 |
-0.769 | 0.454 | N | 0.522 | 0.101 | 0.308904156042 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.88954E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs373308815 |
-0.769 | 0.454 | N | 0.522 | 0.101 | 0.308904156042 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| M/I | rs373308815 |
-0.769 | 0.454 | N | 0.522 | 0.101 | 0.308904156042 | gnomAD-4.0.0 | 5.13495E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.76324E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs2058342072 |
None | 0.891 | N | 0.473 | 0.328 | 0.654164466603 | gnomAD-4.0.0 | 1.59515E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03269E-05 |
| M/V | rs370996945 |
None | 0.454 | N | 0.372 | 0.117 | 0.303781844768 | gnomAD-4.0.0 | 1.59509E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78987E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.6103 | likely_pathogenic | 0.7148 | pathogenic | -1.684 | Destabilizing | 0.688 | D | 0.499 | neutral | None | None | None | None | N |
| M/C | 0.824 | likely_pathogenic | 0.8509 | pathogenic | -1.328 | Destabilizing | 0.998 | D | 0.477 | neutral | None | None | None | None | N |
| M/D | 0.8826 | likely_pathogenic | 0.9253 | pathogenic | -0.383 | Destabilizing | 0.991 | D | 0.588 | neutral | None | None | None | None | N |
| M/E | 0.6118 | likely_pathogenic | 0.6861 | pathogenic | -0.33 | Destabilizing | 0.991 | D | 0.564 | neutral | None | None | None | None | N |
| M/F | 0.3072 | likely_benign | 0.3562 | ambiguous | -0.636 | Destabilizing | 0.842 | D | 0.515 | neutral | None | None | None | None | N |
| M/G | 0.7901 | likely_pathogenic | 0.855 | pathogenic | -2.025 | Highly Destabilizing | 0.991 | D | 0.576 | neutral | None | None | None | None | N |
| M/H | 0.5273 | ambiguous | 0.6325 | pathogenic | -1.066 | Destabilizing | 0.998 | D | 0.541 | neutral | None | None | None | None | N |
| M/I | 0.3197 | likely_benign | 0.3983 | ambiguous | -0.797 | Destabilizing | 0.454 | N | 0.522 | neutral | N | 0.442325517 | None | None | N |
| M/K | 0.2301 | likely_benign | 0.3278 | benign | -0.442 | Destabilizing | 0.891 | D | 0.465 | neutral | N | 0.439845188 | None | None | N |
| M/L | 0.1517 | likely_benign | 0.168 | benign | -0.797 | Destabilizing | 0.002 | N | 0.209 | neutral | N | 0.41266723 | None | None | N |
| M/N | 0.5334 | ambiguous | 0.6716 | pathogenic | -0.384 | Destabilizing | 0.991 | D | 0.563 | neutral | None | None | None | None | N |
| M/P | 0.9653 | likely_pathogenic | 0.9711 | pathogenic | -1.065 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | None | None | N |
| M/Q | 0.3235 | likely_benign | 0.3991 | ambiguous | -0.417 | Destabilizing | 0.991 | D | 0.535 | neutral | None | None | None | None | N |
| M/R | 0.2537 | likely_benign | 0.3141 | benign | -0.038 | Destabilizing | 0.966 | D | 0.508 | neutral | N | 0.440092951 | None | None | N |
| M/S | 0.5658 | likely_pathogenic | 0.6942 | pathogenic | -1.051 | Destabilizing | 0.915 | D | 0.471 | neutral | None | None | None | None | N |
| M/T | 0.3533 | ambiguous | 0.4709 | ambiguous | -0.876 | Destabilizing | 0.891 | D | 0.473 | neutral | N | 0.437753968 | None | None | N |
| M/V | 0.1268 | likely_benign | 0.152 | benign | -1.065 | Destabilizing | 0.454 | N | 0.372 | neutral | N | 0.441452946 | None | None | N |
| M/W | 0.6772 | likely_pathogenic | 0.6933 | pathogenic | -0.591 | Destabilizing | 0.998 | D | 0.493 | neutral | None | None | None | None | N |
| M/Y | 0.5799 | likely_pathogenic | 0.6402 | pathogenic | -0.594 | Destabilizing | 0.974 | D | 0.519 | neutral | 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.