Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28295 | 85108;85109;85110 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| N2AB | 26654 | 80185;80186;80187 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| N2A | 25727 | 77404;77405;77406 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| N2B | 19230 | 57913;57914;57915 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| Novex-1 | 19355 | 58288;58289;58290 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| Novex-2 | 19422 | 58489;58490;58491 | chr2:178561249;178561248;178561247 | chr2:179425976;179425975;179425974 |
| 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 | rs1414095201  |
-0.02 | 1.0 | N | 0.734 | 0.545 | 0.549588557812 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14916E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1414095201 |
-0.02 | 1.0 | N | 0.734 | 0.545 | 0.549588557812 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs1414095201 |
-0.02 | 1.0 | N | 0.734 | 0.545 | 0.549588557812 | gnomAD-4.0.0 | 6.57523E-06 | None | None | None | None | N | None | 2.41418E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2637 | likely_benign | 0.2587 | benign | -0.378 | Destabilizing | 1.0 | D | 0.572 | neutral | N | 0.506165652 | None | None | N |
| P/C | 0.8506 | likely_pathogenic | 0.8448 | pathogenic | -0.746 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| P/D | 0.7304 | likely_pathogenic | 0.7146 | pathogenic | -0.45 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| P/E | 0.5868 | likely_pathogenic | 0.5705 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| P/F | 0.8993 | likely_pathogenic | 0.8947 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/G | 0.5141 | ambiguous | 0.4961 | ambiguous | -0.464 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| P/H | 0.5913 | likely_pathogenic | 0.5871 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/I | 0.7626 | likely_pathogenic | 0.761 | pathogenic | -0.296 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| P/K | 0.6742 | likely_pathogenic | 0.6629 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| P/L | 0.4049 | ambiguous | 0.4085 | ambiguous | -0.296 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.470911031 | None | None | N |
| P/M | 0.7002 | likely_pathogenic | 0.7045 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| P/N | 0.7068 | likely_pathogenic | 0.6926 | pathogenic | -0.245 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/Q | 0.5041 | ambiguous | 0.496 | ambiguous | -0.48 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.463883139 | None | None | N |
| P/R | 0.527 | ambiguous | 0.5241 | ambiguous | 0.051 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.506106937 | None | None | N |
| P/S | 0.4155 | ambiguous | 0.4073 | ambiguous | -0.541 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.499834326 | None | None | N |
| P/T | 0.3155 | likely_benign | 0.3119 | benign | -0.565 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.520382956 | None | None | N |
| P/V | 0.6057 | likely_pathogenic | 0.6063 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| P/W | 0.9299 | likely_pathogenic | 0.9269 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| P/Y | 0.8506 | likely_pathogenic | 0.8479 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | 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.