Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29200 | 87823;87824;87825 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| N2AB | 27559 | 82900;82901;82902 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| N2A | 26632 | 80119;80120;80121 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| N2B | 20135 | 60628;60629;60630 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| Novex-1 | 20260 | 61003;61004;61005 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| Novex-2 | 20327 | 61204;61205;61206 | chr2:178557756;178557755;178557754 | chr2:179422483;179422482;179422481 |
| 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 | rs750362675  |
-0.269 | 0.993 | N | 0.418 | 0.339 | 0.558342666981 | gnomAD-2.1.1 | 2.36976E-04 | None | None | None | None | N | None | 0 | 1.47817E-03 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 1.15932E-03 |
| M/I | rs750362675 |
-0.269 | 0.993 | N | 0.418 | 0.339 | 0.558342666981 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs750362675 |
-0.269 | 0.993 | N | 0.418 | 0.339 | 0.558342666981 | gnomAD-4.0.0 | 4.08963E-05 | None | None | None | None | N | None | 0 | 9.83301E-04 | None | 0 | 0 | None | 0 | 0 | 1.69513E-06 | 0 | 8.00487E-05 |
| M/K | None | None | 0.979 | N | 0.46 | 0.36 | 0.569949186141 | gnomAD-4.0.0 | 6.84168E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65651E-05 |
| M/T | None | None | 0.979 | N | 0.444 | 0.351 | 0.554315986709 | gnomAD-4.0.0 | 2.73667E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 2.31884E-05 | 0 |
| M/V | rs1553554462 |
None | 0.951 | N | 0.444 | 0.259 | 0.520002024791 | 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 |
| M/V | rs1553554462 |
None | 0.951 | N | 0.444 | 0.259 | 0.520002024791 | gnomAD-4.0.0 | 6.56823E-06 | None | None | None | None | N | None | 2.4108E-05 | 0 | None | 0 | 0 | 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 | 0.3576 | ambiguous | 0.3386 | benign | -0.581 | Destabilizing | 0.927 | D | 0.413 | neutral | None | None | None | None | N |
| M/C | 0.6376 | likely_pathogenic | 0.6481 | pathogenic | -0.619 | Destabilizing | 1.0 | D | 0.545 | neutral | None | None | None | None | N |
| M/D | 0.8495 | likely_pathogenic | 0.8459 | pathogenic | 0.337 | Stabilizing | 0.995 | D | 0.631 | neutral | None | None | None | None | N |
| M/E | 0.6735 | likely_pathogenic | 0.6643 | pathogenic | 0.304 | Stabilizing | 0.984 | D | 0.597 | neutral | None | None | None | None | N |
| M/F | 0.4137 | ambiguous | 0.4345 | ambiguous | -0.058 | Destabilizing | 0.999 | D | 0.478 | neutral | None | None | None | None | N |
| M/G | 0.4298 | ambiguous | 0.4082 | ambiguous | -0.784 | Destabilizing | 0.984 | D | 0.575 | neutral | None | None | None | None | N |
| M/H | 0.549 | ambiguous | 0.5703 | pathogenic | 0.151 | Stabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| M/I | 0.4273 | ambiguous | 0.4281 | ambiguous | -0.128 | Destabilizing | 0.993 | D | 0.418 | neutral | N | 0.437807219 | None | None | N |
| M/K | 0.2851 | likely_benign | 0.2689 | benign | 0.289 | Stabilizing | 0.979 | D | 0.46 | neutral | N | 0.391282709 | None | None | N |
| M/L | 0.1274 | likely_benign | 0.1269 | benign | -0.128 | Destabilizing | 0.895 | D | 0.333 | neutral | N | 0.398942187 | None | None | N |
| M/N | 0.4213 | ambiguous | 0.3984 | ambiguous | 0.379 | Stabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| M/P | 0.5475 | ambiguous | 0.5122 | ambiguous | -0.25 | Destabilizing | 0.088 | N | 0.364 | neutral | None | None | None | None | N |
| M/Q | 0.2789 | likely_benign | 0.2807 | benign | 0.248 | Stabilizing | 0.999 | D | 0.471 | neutral | None | None | None | None | N |
| M/R | 0.3071 | likely_benign | 0.2935 | benign | 0.795 | Stabilizing | 0.998 | D | 0.583 | neutral | N | 0.407694956 | None | None | N |
| M/S | 0.3227 | likely_benign | 0.3064 | benign | -0.129 | Destabilizing | 0.984 | D | 0.449 | neutral | None | None | None | None | N |
| M/T | 0.1579 | likely_benign | 0.1408 | benign | -0.053 | Destabilizing | 0.979 | D | 0.444 | neutral | N | 0.32068926 | None | None | N |
| M/V | 0.1251 | likely_benign | 0.1266 | benign | -0.25 | Destabilizing | 0.951 | D | 0.444 | neutral | N | 0.39447773 | None | None | N |
| M/W | 0.68 | likely_pathogenic | 0.6878 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.557 | neutral | None | None | None | None | N |
| M/Y | 0.644 | likely_pathogenic | 0.6462 | pathogenic | 0.088 | Stabilizing | 0.999 | D | 0.577 | 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.