Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28561 | 85906;85907;85908 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| N2AB | 26920 | 80983;80984;80985 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| N2A | 25993 | 78202;78203;78204 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| N2B | 19496 | 58711;58712;58713 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| Novex-1 | 19621 | 59086;59087;59088 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| Novex-2 | 19688 | 59287;59288;59289 | chr2:178560451;178560450;178560449 | chr2:179425178;179425177;179425176 |
| 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/C | rs781472455  |
-0.192 | 1.0 | D | 0.647 | 0.298 | None | gnomAD-2.1.1 | 4.29E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 3.20899E-04 | 2.35E-05 | 1.40924E-04 |
| S/C | rs781472455 |
-0.192 | 1.0 | D | 0.647 | 0.298 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 2.83126E-04 | 0 | 4.41E-05 | 0 | 0 |
| S/C | rs781472455 |
-0.192 | 1.0 | D | 0.647 | 0.298 | None | gnomAD-4.0.0 | 5.51093E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.0851E-04 | 0 | 3.58986E-05 | 0 | 5.69087E-05 |
| S/P | rs1703206822 |
None | 0.997 | N | 0.639 | 0.302 | 0.229924730088 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs1703206822 |
None | 0.997 | N | 0.639 | 0.302 | 0.229924730088 | gnomAD-4.0.0 | 6.57462E-06 | None | None | None | None | N | None | 0 | 6.55308E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0799 | likely_benign | 0.0727 | benign | -0.33 | Destabilizing | 0.219 | N | 0.113 | neutral | N | 0.432246684 | None | None | N |
| S/C | 0.1565 | likely_benign | 0.133 | benign | -0.201 | Destabilizing | 1.0 | D | 0.647 | neutral | D | 0.524100839 | None | None | N |
| S/D | 0.5501 | ambiguous | 0.4929 | ambiguous | 0.224 | Stabilizing | 0.971 | D | 0.533 | neutral | None | None | None | None | N |
| S/E | 0.7274 | likely_pathogenic | 0.6917 | pathogenic | 0.12 | Stabilizing | 0.985 | D | 0.539 | neutral | None | None | None | None | N |
| S/F | 0.3569 | ambiguous | 0.3113 | benign | -0.994 | Destabilizing | 0.999 | D | 0.675 | neutral | N | 0.488689799 | None | None | N |
| S/G | 0.0903 | likely_benign | 0.0811 | benign | -0.416 | Destabilizing | 0.964 | D | 0.577 | neutral | None | None | None | None | N |
| S/H | 0.4709 | ambiguous | 0.4385 | ambiguous | -0.975 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| S/I | 0.3293 | likely_benign | 0.2732 | benign | -0.236 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| S/K | 0.8675 | likely_pathogenic | 0.8362 | pathogenic | -0.331 | Destabilizing | 0.985 | D | 0.533 | neutral | None | None | None | None | N |
| S/L | 0.1432 | likely_benign | 0.1215 | benign | -0.236 | Destabilizing | 0.985 | D | 0.619 | neutral | None | None | None | None | N |
| S/M | 0.2133 | likely_benign | 0.1915 | benign | 0.073 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| S/N | 0.1379 | likely_benign | 0.1181 | benign | -0.045 | Destabilizing | 0.469 | N | 0.241 | neutral | None | None | None | None | N |
| S/P | 0.9375 | likely_pathogenic | 0.8975 | pathogenic | -0.24 | Destabilizing | 0.997 | D | 0.639 | neutral | N | 0.467191729 | None | None | N |
| S/Q | 0.6522 | likely_pathogenic | 0.6173 | pathogenic | -0.325 | Destabilizing | 0.998 | D | 0.573 | neutral | None | None | None | None | N |
| S/R | 0.8351 | likely_pathogenic | 0.8051 | pathogenic | -0.159 | Destabilizing | 0.998 | D | 0.623 | neutral | None | None | None | None | N |
| S/T | 0.1036 | likely_benign | 0.0916 | benign | -0.176 | Destabilizing | 0.98 | D | 0.561 | neutral | N | 0.474768097 | None | None | N |
| S/V | 0.2707 | likely_benign | 0.232 | benign | -0.24 | Destabilizing | 0.985 | D | 0.595 | neutral | None | None | None | None | N |
| S/W | 0.5908 | likely_pathogenic | 0.5453 | ambiguous | -0.997 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| S/Y | 0.2947 | likely_benign | 0.2602 | benign | -0.705 | Destabilizing | 0.999 | D | 0.674 | neutral | N | 0.474308527 | 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.