Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15017 | 45274;45275;45276 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| N2AB | 13376 | 40351;40352;40353 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| N2A | 12449 | 37570;37571;37572 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| N2B | 5952 | 18079;18080;18081 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| Novex-1 | 6077 | 18454;18455;18456 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| Novex-2 | 6144 | 18655;18656;18657 | chr2:178621873;178621872;178621871 | chr2:179486600;179486599;179486598 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.938 | D | 0.399 | 0.352 | 0.469742815239 | gnomAD-4.0.0 | 6.84868E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00045E-07 | 0 | 0 |
| T/R | rs777613831  |
0.063 | 0.984 | N | 0.377 | 0.38 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/R | rs777613831 |
0.063 | 0.984 | N | 0.377 | 0.38 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs777613831 |
0.063 | 0.984 | N | 0.377 | 0.38 | None | gnomAD-4.0.0 | 3.10159E-06 | None | None | None | None | N | None | 5.34645E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48182E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1095 | likely_benign | 0.1056 | benign | -0.165 | Destabilizing | 0.64 | D | 0.468 | neutral | N | 0.505564182 | None | None | N |
| T/C | 0.644 | likely_pathogenic | 0.6307 | pathogenic | -0.543 | Destabilizing | 0.999 | D | 0.414 | neutral | None | None | None | None | N |
| T/D | 0.312 | likely_benign | 0.3189 | benign | -0.046 | Destabilizing | 0.988 | D | 0.4 | neutral | None | None | None | None | N |
| T/E | 0.3037 | likely_benign | 0.2912 | benign | -0.131 | Destabilizing | 0.988 | D | 0.399 | neutral | None | None | None | None | N |
| T/F | 0.376 | ambiguous | 0.3469 | ambiguous | -0.854 | Destabilizing | 0.976 | D | 0.475 | neutral | None | None | None | None | N |
| T/G | 0.2065 | likely_benign | 0.2137 | benign | -0.213 | Destabilizing | 0.034 | N | 0.335 | neutral | None | None | None | None | N |
| T/H | 0.3575 | ambiguous | 0.3457 | ambiguous | -0.323 | Destabilizing | 0.999 | D | 0.495 | neutral | None | None | None | None | N |
| T/I | 0.38 | ambiguous | 0.3509 | ambiguous | -0.157 | Destabilizing | 0.938 | D | 0.399 | neutral | D | 0.545259186 | None | None | N |
| T/K | 0.2804 | likely_benign | 0.2889 | benign | -0.348 | Destabilizing | 0.984 | D | 0.402 | neutral | N | 0.498486533 | None | None | N |
| T/L | 0.1855 | likely_benign | 0.1682 | benign | -0.157 | Destabilizing | 0.662 | D | 0.419 | neutral | None | None | None | None | N |
| T/M | 0.1363 | likely_benign | 0.1211 | benign | -0.31 | Destabilizing | 0.702 | D | 0.435 | neutral | None | None | None | None | N |
| T/N | 0.1193 | likely_benign | 0.1223 | benign | -0.264 | Destabilizing | 0.976 | D | 0.453 | neutral | None | None | None | None | N |
| T/P | 0.1788 | likely_benign | 0.1966 | benign | -0.136 | Destabilizing | 0.995 | D | 0.377 | neutral | N | 0.512203247 | None | None | N |
| T/Q | 0.2964 | likely_benign | 0.294 | benign | -0.422 | Destabilizing | 0.988 | D | 0.373 | neutral | None | None | None | None | N |
| T/R | 0.2596 | likely_benign | 0.245 | benign | -0.066 | Destabilizing | 0.984 | D | 0.377 | neutral | N | 0.50976815 | None | None | N |
| T/S | 0.1362 | likely_benign | 0.1312 | benign | -0.395 | Destabilizing | 0.896 | D | 0.483 | neutral | N | 0.503458134 | None | None | N |
| T/V | 0.2823 | likely_benign | 0.2678 | benign | -0.136 | Destabilizing | 0.851 | D | 0.441 | neutral | None | None | None | None | N |
| T/W | 0.6872 | likely_pathogenic | 0.6762 | pathogenic | -0.969 | Destabilizing | 0.999 | D | 0.536 | neutral | None | None | None | None | N |
| T/Y | 0.3889 | ambiguous | 0.3846 | ambiguous | -0.636 | Destabilizing | 0.988 | D | 0.477 | 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.