Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29224 | 87895;87896;87897 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| N2AB | 27583 | 82972;82973;82974 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| N2A | 26656 | 80191;80192;80193 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| N2B | 20159 | 60700;60701;60702 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| Novex-1 | 20284 | 61075;61076;61077 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| Novex-2 | 20351 | 61276;61277;61278 | chr2:178557684;178557683;178557682 | chr2:179422411;179422410;179422409 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs878915392  |
-2.323 | 0.001 | N | 0.488 | 0.254 | 0.514587094315 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs878915392 |
-2.323 | 0.001 | N | 0.488 | 0.254 | 0.514587094315 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs878915392 |
-2.323 | 0.001 | N | 0.488 | 0.254 | 0.514587094315 | gnomAD-4.0.0 | 4.33743E-06 | None | None | None | None | N | None | 5.3376E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69511E-06 | 1.09791E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.147 | likely_benign | 0.2858 | benign | -2.12 | Highly Destabilizing | 0.057 | N | 0.663 | prob.neutral | None | None | None | None | N |
| I/C | 0.5209 | ambiguous | 0.6958 | pathogenic | -1.274 | Destabilizing | 0.887 | D | 0.641 | neutral | None | None | None | None | N |
| I/D | 0.7987 | likely_pathogenic | 0.9338 | pathogenic | -1.97 | Destabilizing | 0.507 | D | 0.762 | deleterious | None | None | None | None | N |
| I/E | 0.613 | likely_pathogenic | 0.8165 | pathogenic | -1.883 | Destabilizing | 0.507 | D | 0.738 | deleterious | None | None | None | None | N |
| I/F | 0.2652 | likely_benign | 0.4456 | ambiguous | -1.376 | Destabilizing | 0.34 | N | 0.679 | prob.neutral | None | None | None | None | N |
| I/G | 0.5541 | ambiguous | 0.7942 | pathogenic | -2.54 | Highly Destabilizing | 0.507 | D | 0.72 | deleterious | None | None | None | None | N |
| I/H | 0.6282 | likely_pathogenic | 0.8248 | pathogenic | -1.865 | Destabilizing | 0.96 | D | 0.776 | deleterious | None | None | None | None | N |
| I/K | 0.439 | ambiguous | 0.6554 | pathogenic | -1.579 | Destabilizing | 0.437 | N | 0.729 | deleterious | N | 0.513025415 | None | None | N |
| I/L | 0.066 | likely_benign | 0.0829 | benign | -0.979 | Destabilizing | None | N | 0.199 | neutral | N | 0.366587413 | None | None | N |
| I/M | 0.0816 | likely_benign | 0.1055 | benign | -0.74 | Destabilizing | 0.437 | N | 0.631 | neutral | N | 0.520047388 | None | None | N |
| I/N | 0.3923 | ambiguous | 0.6513 | pathogenic | -1.539 | Destabilizing | 0.507 | D | 0.772 | deleterious | None | None | None | None | N |
| I/P | 0.8911 | likely_pathogenic | 0.9651 | pathogenic | -1.332 | Destabilizing | 0.676 | D | 0.771 | deleterious | None | None | None | None | N |
| I/Q | 0.4548 | ambiguous | 0.6699 | pathogenic | -1.621 | Destabilizing | 0.676 | D | 0.781 | deleterious | None | None | None | None | N |
| I/R | 0.3395 | likely_benign | 0.5495 | ambiguous | -1.048 | Destabilizing | 0.437 | N | 0.783 | deleterious | N | 0.520740821 | None | None | N |
| I/S | 0.2194 | likely_benign | 0.424 | ambiguous | -2.18 | Highly Destabilizing | 0.128 | N | 0.654 | prob.neutral | None | None | None | None | N |
| I/T | 0.068 | likely_benign | 0.1339 | benign | -1.971 | Destabilizing | 0.001 | N | 0.488 | neutral | N | 0.476680612 | None | None | N |
| I/V | 0.0677 | likely_benign | 0.0857 | benign | -1.332 | Destabilizing | 0.001 | N | 0.164 | neutral | N | 0.460748368 | None | None | N |
| I/W | 0.8247 | likely_pathogenic | 0.931 | pathogenic | -1.609 | Destabilizing | 0.96 | D | 0.784 | deleterious | None | None | None | None | N |
| I/Y | 0.6709 | likely_pathogenic | 0.8458 | pathogenic | -1.357 | Destabilizing | 0.676 | D | 0.717 | prob.delet. | 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.