Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3356 | 10291;10292;10293 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| N2AB | 3356 | 10291;10292;10293 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| N2A | 3356 | 10291;10292;10293 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| N2B | 3310 | 10153;10154;10155 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| Novex-1 | 3310 | 10153;10154;10155 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| Novex-2 | 3310 | 10153;10154;10155 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
| Novex-3 | 3356 | 10291;10292;10293 | chr2:178764225;178764224;178764223 | chr2:179628952;179628951;179628950 |
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 | rs763323132  |
-0.305 | 0.852 | N | 0.411 | 0.255 | 0.43126412278 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 1.23031E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.8E-06 | 0 |
| T/I | rs763323132 |
-0.305 | 0.852 | N | 0.411 | 0.255 | 0.43126412278 | gnomAD-4.0.0 | 3.42046E-06 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.5973E-06 | 0 | 0 |
| T/S | None | None | 0.704 | N | 0.431 | 0.192 | 0.254761474806 | gnomAD-4.0.0 | 6.84092E-07 | None | None | None | None | N | None | 2.98704E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1123 | likely_benign | 0.1131 | benign | -0.989 | Destabilizing | 0.061 | N | 0.129 | neutral | N | 0.414064384 | None | None | N |
| T/C | 0.5439 | ambiguous | 0.4486 | ambiguous | -0.824 | Destabilizing | 0.999 | D | 0.469 | neutral | None | None | None | None | N |
| T/D | 0.8822 | likely_pathogenic | 0.8846 | pathogenic | -1.086 | Destabilizing | 0.991 | D | 0.477 | neutral | None | None | None | None | N |
| T/E | 0.8209 | likely_pathogenic | 0.807 | pathogenic | -1.038 | Destabilizing | 0.969 | D | 0.458 | neutral | None | None | None | None | N |
| T/F | 0.6372 | likely_pathogenic | 0.5566 | ambiguous | -0.966 | Destabilizing | 0.991 | D | 0.483 | neutral | None | None | None | None | N |
| T/G | 0.514 | ambiguous | 0.531 | ambiguous | -1.278 | Destabilizing | 0.884 | D | 0.383 | neutral | None | None | None | None | N |
| T/H | 0.7055 | likely_pathogenic | 0.6616 | pathogenic | -1.52 | Destabilizing | 0.999 | D | 0.467 | neutral | None | None | None | None | N |
| T/I | 0.2871 | likely_benign | 0.2235 | benign | -0.292 | Destabilizing | 0.852 | D | 0.411 | neutral | N | 0.480583465 | None | None | N |
| T/K | 0.6585 | likely_pathogenic | 0.6113 | pathogenic | -0.805 | Destabilizing | 0.939 | D | 0.447 | neutral | None | None | None | None | N |
| T/L | 0.227 | likely_benign | 0.2033 | benign | -0.292 | Destabilizing | 0.759 | D | 0.357 | neutral | None | None | None | None | N |
| T/M | 0.1775 | likely_benign | 0.1518 | benign | -0.01 | Destabilizing | 0.991 | D | 0.475 | neutral | None | None | None | None | N |
| T/N | 0.4952 | ambiguous | 0.4768 | ambiguous | -0.969 | Destabilizing | 0.996 | D | 0.513 | neutral | N | 0.512741498 | None | None | N |
| T/P | 0.6651 | likely_pathogenic | 0.6462 | pathogenic | -0.494 | Destabilizing | 0.988 | D | 0.476 | neutral | D | 0.544244332 | None | None | N |
| T/Q | 0.6685 | likely_pathogenic | 0.6225 | pathogenic | -1.158 | Destabilizing | 0.997 | D | 0.488 | neutral | None | None | None | None | N |
| T/R | 0.5186 | ambiguous | 0.4614 | ambiguous | -0.591 | Destabilizing | 0.991 | D | 0.489 | neutral | None | None | None | None | N |
| T/S | 0.2494 | likely_benign | 0.2406 | benign | -1.197 | Destabilizing | 0.704 | D | 0.431 | neutral | N | 0.5112759 | None | None | N |
| T/V | 0.203 | likely_benign | 0.1545 | benign | -0.494 | Destabilizing | 0.17 | N | 0.195 | neutral | None | None | None | None | N |
| T/W | 0.9364 | likely_pathogenic | 0.9074 | pathogenic | -0.916 | Destabilizing | 0.999 | D | 0.511 | neutral | None | None | None | None | N |
| T/Y | 0.7651 | likely_pathogenic | 0.7026 | pathogenic | -0.641 | Destabilizing | 0.997 | D | 0.483 | 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.