Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29181 | 87766;87767;87768 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| N2AB | 27540 | 82843;82844;82845 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| N2A | 26613 | 80062;80063;80064 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| N2B | 20116 | 60571;60572;60573 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| Novex-1 | 20241 | 60946;60947;60948 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| Novex-2 | 20308 | 61147;61148;61149 | chr2:178557813;178557812;178557811 | chr2:179422540;179422539;179422538 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.027 | N | 0.243 | 0.215 | 0.210429274316 | gnomAD-4.0.0 | 1.36832E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79886E-06 | 0 | 0 |
| S/N | rs768624965  |
0.109 | None | N | 0.216 | 0.091 | 0.159798565429 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| S/N | rs768624965 |
0.109 | None | N | 0.216 | 0.091 | 0.159798565429 | gnomAD-4.0.0 | 4.10499E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39659E-06 | 0 | 0 |
| S/R | rs776861234 |
0.107 | 0.317 | N | 0.249 | 0.258 | 0.297718772494 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| S/R | rs776861234 |
0.107 | 0.317 | N | 0.249 | 0.258 | 0.297718772494 | 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 |
| S/R | rs776861234 |
0.107 | 0.317 | N | 0.249 | 0.258 | 0.297718772494 | gnomAD-4.0.0 | 1.23926E-06 | None | None | None | None | N | None | 1.33444E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47562E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.09 | likely_benign | 0.0923 | benign | -0.192 | Destabilizing | 0.035 | N | 0.231 | neutral | None | None | None | None | N |
| S/C | 0.1432 | likely_benign | 0.1699 | benign | -0.366 | Destabilizing | 0.78 | D | 0.271 | neutral | N | 0.49536207 | None | None | N |
| S/D | 0.3376 | likely_benign | 0.4751 | ambiguous | -0.036 | Destabilizing | 0.081 | N | 0.206 | neutral | None | None | None | None | N |
| S/E | 0.5414 | ambiguous | 0.6612 | pathogenic | -0.15 | Destabilizing | 0.149 | N | 0.206 | neutral | None | None | None | None | N |
| S/F | 0.4172 | ambiguous | 0.441 | ambiguous | -0.948 | Destabilizing | 0.555 | D | 0.384 | neutral | None | None | None | None | N |
| S/G | 0.0743 | likely_benign | 0.0805 | benign | -0.22 | Destabilizing | 0.027 | N | 0.243 | neutral | N | 0.421200184 | None | None | N |
| S/H | 0.3325 | likely_benign | 0.4485 | ambiguous | -0.567 | Destabilizing | 0.38 | N | 0.247 | neutral | None | None | None | None | N |
| S/I | 0.2717 | likely_benign | 0.341 | ambiguous | -0.249 | Destabilizing | 0.188 | N | 0.363 | neutral | N | 0.47996684 | None | None | N |
| S/K | 0.6009 | likely_pathogenic | 0.7201 | pathogenic | -0.366 | Destabilizing | 0.081 | N | 0.205 | neutral | None | None | None | None | N |
| S/L | 0.179 | likely_benign | 0.179 | benign | -0.249 | Destabilizing | 0.081 | N | 0.309 | neutral | None | None | None | None | N |
| S/M | 0.2764 | likely_benign | 0.3046 | benign | -0.141 | Destabilizing | 0.824 | D | 0.25 | neutral | None | None | None | None | N |
| S/N | 0.1112 | likely_benign | 0.1361 | benign | -0.137 | Destabilizing | None | N | 0.216 | neutral | N | 0.496524662 | None | None | N |
| S/P | 0.5636 | ambiguous | 0.6522 | pathogenic | -0.208 | Destabilizing | 0.555 | D | 0.255 | neutral | None | None | None | None | N |
| S/Q | 0.4776 | ambiguous | 0.5792 | pathogenic | -0.381 | Destabilizing | 0.38 | N | 0.228 | neutral | None | None | None | None | N |
| S/R | 0.5533 | ambiguous | 0.6567 | pathogenic | -0.128 | Destabilizing | 0.317 | N | 0.249 | neutral | N | 0.510803468 | None | None | N |
| S/T | 0.0841 | likely_benign | 0.0879 | benign | -0.258 | Destabilizing | None | N | 0.112 | neutral | N | 0.42559007 | None | None | N |
| S/V | 0.2302 | likely_benign | 0.2901 | benign | -0.208 | Destabilizing | 0.081 | N | 0.295 | neutral | None | None | None | None | N |
| S/W | 0.5783 | likely_pathogenic | 0.6232 | pathogenic | -1.022 | Destabilizing | 0.935 | D | 0.48 | neutral | None | None | None | None | N |
| S/Y | 0.3454 | ambiguous | 0.3894 | ambiguous | -0.711 | Destabilizing | 0.555 | D | 0.383 | 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.