Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13991 | 42196;42197;42198 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| N2AB | 12350 | 37273;37274;37275 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| N2A | 11423 | 34492;34493;34494 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| N2B | 4926 | 15001;15002;15003 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| Novex-1 | 5051 | 15376;15377;15378 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| Novex-2 | 5118 | 15577;15578;15579 | chr2:178635218;178635217;178635216 | chr2:179499945;179499944;179499943 |
| 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/S | rs1247699000  |
-0.589 | 0.006 | N | 0.243 | 0.059 | 0.0716867268079 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| A/S | rs1247699000 |
-0.589 | 0.006 | N | 0.243 | 0.059 | 0.0716867268079 | gnomAD-4.0.0 | 1.5923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88296E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5759 | likely_pathogenic | 0.6048 | pathogenic | -0.88 | Destabilizing | 0.492 | N | 0.445 | neutral | None | None | None | None | N |
| A/D | 0.1281 | likely_benign | 0.1271 | benign | -0.627 | Destabilizing | None | N | 0.132 | neutral | None | None | None | None | N |
| A/E | 0.0978 | likely_benign | 0.1088 | benign | -0.765 | Destabilizing | None | N | 0.123 | neutral | N | 0.360712116 | None | None | N |
| A/F | 0.354 | ambiguous | 0.3876 | ambiguous | -1.125 | Destabilizing | 0.112 | N | 0.541 | neutral | None | None | None | None | N |
| A/G | 0.141 | likely_benign | 0.1376 | benign | -0.648 | Destabilizing | 0.011 | N | 0.183 | neutral | N | 0.431729524 | None | None | N |
| A/H | 0.4477 | ambiguous | 0.4393 | ambiguous | -0.72 | Destabilizing | 0.204 | N | 0.503 | neutral | None | None | None | None | N |
| A/I | 0.1646 | likely_benign | 0.1934 | benign | -0.505 | Destabilizing | 0.006 | N | 0.499 | neutral | None | None | None | None | N |
| A/K | 0.3527 | ambiguous | 0.3264 | benign | -0.77 | Destabilizing | 0.007 | N | 0.378 | neutral | None | None | None | None | N |
| A/L | 0.1534 | likely_benign | 0.1609 | benign | -0.505 | Destabilizing | 0.007 | N | 0.359 | neutral | None | None | None | None | N |
| A/M | 0.1701 | likely_benign | 0.1853 | benign | -0.408 | Destabilizing | 0.112 | N | 0.403 | neutral | None | None | None | None | N |
| A/N | 0.1607 | likely_benign | 0.156 | benign | -0.474 | Destabilizing | 0.018 | N | 0.479 | neutral | None | None | None | None | N |
| A/P | 0.1664 | likely_benign | 0.1308 | benign | -0.487 | Destabilizing | None | N | 0.229 | neutral | N | 0.383107252 | None | None | N |
| A/Q | 0.22 | likely_benign | 0.2163 | benign | -0.769 | Destabilizing | None | N | 0.274 | neutral | None | None | None | None | N |
| A/R | 0.417 | ambiguous | 0.4145 | ambiguous | -0.321 | Destabilizing | 0.018 | N | 0.499 | neutral | None | None | None | None | N |
| A/S | 0.0892 | likely_benign | 0.0871 | benign | -0.723 | Destabilizing | 0.006 | N | 0.243 | neutral | N | 0.431174012 | None | None | N |
| A/T | 0.0761 | likely_benign | 0.083 | benign | -0.779 | Destabilizing | 0.006 | N | 0.213 | neutral | N | 0.432743017 | None | None | N |
| A/V | 0.089 | likely_benign | 0.1054 | benign | -0.487 | Destabilizing | None | N | 0.131 | neutral | N | 0.437718425 | None | None | N |
| A/W | 0.7412 | likely_pathogenic | 0.7515 | pathogenic | -1.262 | Destabilizing | 0.747 | D | 0.571 | neutral | None | None | None | None | N |
| A/Y | 0.4596 | ambiguous | 0.4646 | ambiguous | -0.906 | Destabilizing | 0.204 | N | 0.567 | 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.