Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35164 | 105715;105716;105717 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| N2AB | 33523 | 100792;100793;100794 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| N2A | 32596 | 98011;98012;98013 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| N2B | 26099 | 78520;78521;78522 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| Novex-1 | 26224 | 78895;78896;78897 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| Novex-2 | 26291 | 79096;79097;79098 | chr2:178531125;178531124;178531123 | chr2:179395852;179395851;179395850 |
| 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/C | rs200123047  |
-1.475 | 0.028 | N | 0.477 | 0.402 | 0.424549175451 | gnomAD-2.1.1 | 5.35E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 3.26776E-04 | None | 0 | 2.34E-05 | 0 |
| R/C | rs200123047 |
-1.475 | 0.028 | N | 0.477 | 0.402 | 0.424549175451 | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 3.85802E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/C | rs200123047 |
-1.475 | 0.028 | N | 0.477 | 0.402 | 0.424549175451 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/C | rs200123047 |
-1.475 | 0.028 | N | 0.477 | 0.402 | 0.424549175451 | gnomAD-4.0.0 | 5.39054E-05 | None | None | None | None | N | None | 7.99659E-05 | 0 | None | 0 | 6.68568E-05 | None | 0 | 3.29924E-04 | 3.55967E-05 | 2.7452E-04 | 1.44028E-04 |
| R/H | rs768358201 |
-2.031 | 0.005 | N | 0.169 | 0.129 | 0.101711395817 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 1.29166E-04 | 2.9E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.66E-05 | 0 |
| R/H | rs768358201 |
-2.031 | 0.005 | N | 0.169 | 0.129 | 0.101711395817 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs768358201 |
-2.031 | 0.005 | N | 0.169 | 0.129 | 0.101711395817 | gnomAD-4.0.0 | 4.15155E-05 | None | None | None | None | N | None | 1.33501E-05 | 3.33367E-05 | None | 0 | 0 | None | 0 | 0 | 4.49193E-05 | 7.68521E-05 | 6.40328E-05 |
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 | 0.5212 | ambiguous | 0.5518 | ambiguous | -1.253 | Destabilizing | 0.16 | N | 0.457 | neutral | None | None | None | None | N |
| R/C | 0.129 | likely_benign | 0.1508 | benign | -1.112 | Destabilizing | 0.028 | N | 0.477 | neutral | N | 0.496436982 | None | None | N |
| R/D | 0.7829 | likely_pathogenic | 0.7861 | pathogenic | -0.236 | Destabilizing | 0.652 | D | 0.573 | neutral | None | None | None | None | N |
| R/E | 0.4542 | ambiguous | 0.4689 | ambiguous | -0.052 | Destabilizing | 0.16 | N | 0.423 | neutral | None | None | None | None | N |
| R/F | 0.5821 | likely_pathogenic | 0.6257 | pathogenic | -0.826 | Destabilizing | 0.317 | N | 0.663 | neutral | None | None | None | None | N |
| R/G | 0.3534 | ambiguous | 0.3654 | ambiguous | -1.617 | Destabilizing | 0.782 | D | 0.552 | neutral | N | 0.478079238 | None | None | N |
| R/H | 0.092 | likely_benign | 0.1012 | benign | -1.85 | Destabilizing | 0.005 | N | 0.169 | neutral | N | 0.454075033 | None | None | N |
| R/I | 0.3761 | ambiguous | 0.4082 | ambiguous | -0.24 | Destabilizing | 0.764 | D | 0.662 | neutral | None | None | None | None | N |
| R/K | 0.1476 | likely_benign | 0.1415 | benign | -0.878 | Destabilizing | 0.16 | N | 0.43 | neutral | None | None | None | None | N |
| R/L | 0.2515 | likely_benign | 0.28 | benign | -0.24 | Destabilizing | 0.268 | N | 0.519 | neutral | N | 0.513275265 | None | None | N |
| R/M | 0.4106 | ambiguous | 0.4369 | ambiguous | -0.633 | Destabilizing | 0.952 | D | 0.599 | neutral | None | None | None | None | N |
| R/N | 0.6299 | likely_pathogenic | 0.6385 | pathogenic | -0.61 | Destabilizing | 0.481 | N | 0.433 | neutral | None | None | None | None | N |
| R/P | 0.89 | likely_pathogenic | 0.8608 | pathogenic | -0.559 | Destabilizing | 0.975 | D | 0.655 | neutral | N | 0.507793288 | None | None | N |
| R/Q | 0.095 | likely_benign | 0.1026 | benign | -0.642 | Destabilizing | 0.035 | N | 0.319 | neutral | None | None | None | None | N |
| R/S | 0.5316 | ambiguous | 0.5644 | pathogenic | -1.49 | Destabilizing | 0.639 | D | 0.541 | neutral | N | 0.461696503 | None | None | N |
| R/T | 0.4385 | ambiguous | 0.4478 | ambiguous | -1.084 | Destabilizing | 0.481 | N | 0.532 | neutral | None | None | None | None | N |
| R/V | 0.4705 | ambiguous | 0.5098 | ambiguous | -0.559 | Destabilizing | 0.481 | N | 0.586 | neutral | None | None | None | None | N |
| R/W | 0.1558 | likely_benign | 0.1827 | benign | -0.388 | Destabilizing | 0.987 | D | 0.642 | neutral | None | None | None | None | N |
| R/Y | 0.3439 | ambiguous | 0.3907 | ambiguous | -0.167 | Destabilizing | 0.012 | N | 0.453 | 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.