Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23637 | 71134;71135;71136 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| N2AB | 21996 | 66211;66212;66213 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| N2A | 21069 | 63430;63431;63432 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| N2B | 14572 | 43939;43940;43941 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| Novex-1 | 14697 | 44314;44315;44316 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| Novex-2 | 14764 | 44515;44516;44517 | chr2:178575223;178575222;178575221 | chr2:179439950;179439949;179439948 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs772116474  |
None | 0.014 | N | 0.258 | 0.268 | 0.1749357433 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| G/S | rs1243986262 |
-0.398 | 0.153 | N | 0.191 | 0.143 | 0.152612264143 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/S | rs1243986262 |
-0.398 | 0.153 | N | 0.191 | 0.143 | 0.152612264143 | gnomAD-4.0.0 | 1.36925E-06 | None | None | None | None | I | None | 0 | 2.24054E-05 | None | 0 | 0 | None | 0 | 0 | 8.99722E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.2047 | likely_benign | 0.2256 | benign | -0.786 | Destabilizing | 0.014 | N | 0.195 | neutral | N | 0.463327313 | None | None | I |
| G/C | 0.3517 | ambiguous | 0.3582 | ambiguous | -1.315 | Destabilizing | 0.997 | D | 0.575 | neutral | N | 0.465407613 | None | None | I |
| G/D | 0.3304 | likely_benign | 0.3694 | ambiguous | -0.82 | Destabilizing | 0.014 | N | 0.258 | neutral | N | 0.415805512 | None | None | I |
| G/E | 0.3576 | ambiguous | 0.4147 | ambiguous | -0.93 | Destabilizing | 0.754 | D | 0.435 | neutral | None | None | None | None | I |
| G/F | 0.726 | likely_pathogenic | 0.7743 | pathogenic | -1.324 | Destabilizing | 0.978 | D | 0.556 | neutral | None | None | None | None | I |
| G/H | 0.5456 | ambiguous | 0.5825 | pathogenic | -0.578 | Destabilizing | 0.998 | D | 0.516 | neutral | None | None | None | None | I |
| G/I | 0.4847 | ambiguous | 0.5477 | ambiguous | -0.984 | Destabilizing | 0.956 | D | 0.552 | neutral | None | None | None | None | I |
| G/K | 0.6799 | likely_pathogenic | 0.7168 | pathogenic | -0.994 | Destabilizing | 0.956 | D | 0.417 | neutral | None | None | None | None | I |
| G/L | 0.602 | likely_pathogenic | 0.654 | pathogenic | -0.984 | Destabilizing | 0.956 | D | 0.495 | neutral | None | None | None | None | I |
| G/M | 0.6058 | likely_pathogenic | 0.6573 | pathogenic | -1.202 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | I |
| G/N | 0.287 | likely_benign | 0.3107 | benign | -0.798 | Destabilizing | 0.754 | D | 0.295 | neutral | None | None | None | None | I |
| G/P | 0.8371 | likely_pathogenic | 0.862 | pathogenic | -0.902 | Destabilizing | 0.978 | D | 0.489 | neutral | None | None | None | None | I |
| G/Q | 0.5228 | ambiguous | 0.562 | ambiguous | -0.983 | Destabilizing | 0.978 | D | 0.488 | neutral | None | None | None | None | I |
| G/R | 0.5816 | likely_pathogenic | 0.624 | pathogenic | -0.605 | Destabilizing | 0.97 | D | 0.492 | neutral | N | 0.464194105 | None | None | I |
| G/S | 0.1367 | likely_benign | 0.1442 | benign | -1.007 | Destabilizing | 0.153 | N | 0.191 | neutral | N | 0.426155792 | None | None | I |
| G/T | 0.2285 | likely_benign | 0.2542 | benign | -1.058 | Destabilizing | 0.754 | D | 0.434 | neutral | None | None | None | None | I |
| G/V | 0.328 | likely_benign | 0.3686 | ambiguous | -0.902 | Destabilizing | 0.89 | D | 0.498 | neutral | N | 0.464887538 | None | None | I |
| G/W | 0.6215 | likely_pathogenic | 0.6524 | pathogenic | -1.322 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | I |
| G/Y | 0.5837 | likely_pathogenic | 0.6338 | pathogenic | -1.145 | Destabilizing | 0.993 | D | 0.561 | 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.