Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13994 | 42205;42206;42207 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| N2AB | 12353 | 37282;37283;37284 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| N2A | 11426 | 34501;34502;34503 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| N2B | 4929 | 15010;15011;15012 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| Novex-1 | 5054 | 15385;15386;15387 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| Novex-2 | 5121 | 15586;15587;15588 | chr2:178635209;178635208;178635207 | chr2:179499936;179499935;179499934 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1380914730  |
-0.094 | 0.278 | N | 0.429 | 0.21 | 0.20549828249 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| P/L | rs1380914730 |
-0.094 | 0.278 | N | 0.429 | 0.21 | 0.20549828249 | gnomAD-4.0.0 | 1.36881E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99669E-07 | 1.15974E-05 | 0 |
| P/S | rs201232835 |
-0.485 | 0.483 | N | 0.344 | 0.152 | None | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 4.97611E-04 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/S | rs201232835 |
-0.485 | 0.483 | N | 0.344 | 0.152 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 5.76037E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs201232835 |
-0.485 | 0.483 | N | 0.344 | 0.152 | None | gnomAD-4.0.0 | 1.17782E-05 | None | None | None | None | N | None | 1.33568E-05 | 3.33611E-05 | None | 3.71797E-04 | 0 | None | 0 | 0 | 8.47813E-07 | 0 | 6.40779E-05 |
| P/T | rs201232835 |
-0.491 | 0.651 | N | 0.321 | 0.086 | 0.156986980423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs201232835 |
-0.491 | 0.651 | N | 0.321 | 0.086 | 0.156986980423 | gnomAD-4.0.0 | 1.36883E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.04668E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1085 | likely_benign | 0.0954 | benign | -0.612 | Destabilizing | 0.002 | N | 0.191 | neutral | N | 0.443194217 | None | None | N |
| P/C | 0.8518 | likely_pathogenic | 0.8051 | pathogenic | -0.615 | Destabilizing | 0.985 | D | 0.454 | neutral | None | None | None | None | N |
| P/D | 0.6187 | likely_pathogenic | 0.5348 | ambiguous | -0.61 | Destabilizing | 0.834 | D | 0.414 | neutral | None | None | None | None | N |
| P/E | 0.3992 | ambiguous | 0.3422 | ambiguous | -0.698 | Destabilizing | 0.712 | D | 0.404 | neutral | None | None | None | None | N |
| P/F | 0.8059 | likely_pathogenic | 0.7312 | pathogenic | -0.737 | Destabilizing | 0.946 | D | 0.521 | neutral | None | None | None | None | N |
| P/G | 0.5997 | likely_pathogenic | 0.4808 | ambiguous | -0.776 | Destabilizing | 0.553 | D | 0.359 | neutral | None | None | None | None | N |
| P/H | 0.5212 | ambiguous | 0.4201 | ambiguous | -0.329 | Destabilizing | 0.013 | N | 0.361 | neutral | N | 0.435311195 | None | None | N |
| P/I | 0.5139 | ambiguous | 0.4495 | ambiguous | -0.311 | Destabilizing | 0.032 | N | 0.432 | neutral | None | None | None | None | N |
| P/K | 0.6815 | likely_pathogenic | 0.5517 | ambiguous | -0.614 | Destabilizing | 0.712 | D | 0.416 | neutral | None | None | None | None | N |
| P/L | 0.261 | likely_benign | 0.2085 | benign | -0.311 | Destabilizing | 0.278 | N | 0.429 | neutral | N | 0.417207979 | None | None | N |
| P/M | 0.5744 | likely_pathogenic | 0.4899 | ambiguous | -0.427 | Destabilizing | 0.946 | D | 0.428 | neutral | None | None | None | None | N |
| P/N | 0.6163 | likely_pathogenic | 0.4948 | ambiguous | -0.352 | Destabilizing | 0.897 | D | 0.433 | neutral | None | None | None | None | N |
| P/Q | 0.354 | ambiguous | 0.2648 | benign | -0.575 | Destabilizing | 0.946 | D | 0.416 | neutral | None | None | None | None | N |
| P/R | 0.5435 | ambiguous | 0.4269 | ambiguous | -0.088 | Destabilizing | 0.93 | D | 0.442 | neutral | N | 0.481293446 | None | None | N |
| P/S | 0.2631 | likely_benign | 0.1949 | benign | -0.678 | Destabilizing | 0.483 | N | 0.344 | neutral | N | 0.478558151 | None | None | N |
| P/T | 0.2142 | likely_benign | 0.1624 | benign | -0.665 | Destabilizing | 0.651 | D | 0.321 | neutral | N | 0.424285405 | None | None | N |
| P/V | 0.3579 | ambiguous | 0.305 | benign | -0.377 | Destabilizing | 0.338 | N | 0.339 | neutral | None | None | None | None | N |
| P/W | 0.9229 | likely_pathogenic | 0.8845 | pathogenic | -0.847 | Destabilizing | 0.995 | D | 0.569 | neutral | None | None | None | None | N |
| P/Y | 0.7969 | likely_pathogenic | 0.7213 | pathogenic | -0.551 | Destabilizing | 0.897 | D | 0.489 | 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.