Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23615 | 71068;71069;71070 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| N2AB | 21974 | 66145;66146;66147 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| N2A | 21047 | 63364;63365;63366 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| N2B | 14550 | 43873;43874;43875 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| Novex-1 | 14675 | 44248;44249;44250 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| Novex-2 | 14742 | 44449;44450;44451 | chr2:178575289;178575288;178575287 | chr2:179440016;179440015;179440014 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs574614034  |
-0.858 | 0.491 | N | 0.363 | 0.186 | 0.20549828249 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| A/T | rs574614034 |
-0.858 | 0.491 | N | 0.363 | 0.186 | 0.20549828249 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/T | rs574614034 |
-0.858 | 0.491 | N | 0.363 | 0.186 | 0.20549828249 | gnomAD-4.0.0 | 2.47953E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54326E-06 | 1.09827E-05 | 0 |
| A/V | None | None | 0.166 | N | 0.372 | 0.097 | 0.283761946502 | gnomAD-4.0.0 | 2.40068E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62504E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4434 | ambiguous | 0.4563 | ambiguous | -0.791 | Destabilizing | 0.991 | D | 0.532 | neutral | None | None | None | None | N |
| A/D | 0.1429 | likely_benign | 0.1421 | benign | -1.039 | Destabilizing | None | N | 0.259 | neutral | N | 0.368389993 | None | None | N |
| A/E | 0.1453 | likely_benign | 0.1516 | benign | -1.191 | Destabilizing | 0.007 | N | 0.206 | neutral | None | None | None | None | N |
| A/F | 0.2592 | likely_benign | 0.2512 | benign | -1.25 | Destabilizing | 0.818 | D | 0.596 | neutral | None | None | None | None | N |
| A/G | 0.1397 | likely_benign | 0.1529 | benign | -0.773 | Destabilizing | 0.285 | N | 0.363 | neutral | N | 0.473207872 | None | None | N |
| A/H | 0.315 | likely_benign | 0.3179 | benign | -0.772 | Destabilizing | 0.965 | D | 0.594 | neutral | None | None | None | None | N |
| A/I | 0.1503 | likely_benign | 0.1565 | benign | -0.64 | Destabilizing | 0.39 | N | 0.555 | neutral | None | None | None | None | N |
| A/K | 0.2841 | likely_benign | 0.3049 | benign | -0.956 | Destabilizing | 0.561 | D | 0.523 | neutral | None | None | None | None | N |
| A/L | 0.1053 | likely_benign | 0.1091 | benign | -0.64 | Destabilizing | 0.004 | N | 0.225 | neutral | None | None | None | None | N |
| A/M | 0.1585 | likely_benign | 0.1661 | benign | -0.408 | Destabilizing | 0.818 | D | 0.585 | neutral | None | None | None | None | N |
| A/N | 0.1536 | likely_benign | 0.1554 | benign | -0.574 | Destabilizing | 0.39 | N | 0.603 | neutral | None | None | None | None | N |
| A/P | 0.1187 | likely_benign | 0.1262 | benign | -0.621 | Destabilizing | 0.662 | D | 0.644 | neutral | N | 0.399382117 | None | None | N |
| A/Q | 0.2019 | likely_benign | 0.2133 | benign | -0.933 | Destabilizing | 0.561 | D | 0.645 | neutral | None | None | None | None | N |
| A/R | 0.3171 | likely_benign | 0.3271 | benign | -0.373 | Destabilizing | 0.561 | D | 0.641 | neutral | None | None | None | None | N |
| A/S | 0.0797 | likely_benign | 0.0799 | benign | -0.768 | Destabilizing | 0.285 | N | 0.383 | neutral | N | 0.470207639 | None | None | N |
| A/T | 0.0769 | likely_benign | 0.0797 | benign | -0.853 | Destabilizing | 0.491 | N | 0.363 | neutral | N | 0.474248022 | None | None | N |
| A/V | 0.0888 | likely_benign | 0.0922 | benign | -0.621 | Destabilizing | 0.166 | N | 0.372 | neutral | N | 0.472266509 | None | None | N |
| A/W | 0.6252 | likely_pathogenic | 0.621 | pathogenic | -1.363 | Destabilizing | 0.991 | D | 0.663 | neutral | None | None | None | None | N |
| A/Y | 0.3369 | likely_benign | 0.3353 | benign | -1.044 | Destabilizing | 0.901 | D | 0.603 | 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.