Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22314 | 67165;67166;67167 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| N2AB | 20673 | 62242;62243;62244 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| N2A | 19746 | 59461;59462;59463 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| N2B | 13249 | 39970;39971;39972 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| Novex-1 | 13374 | 40345;40346;40347 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| Novex-2 | 13441 | 40546;40547;40548 | chr2:178580439;178580438;178580437 | chr2:179445166;179445165;179445164 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.02 | N | 0.243 | 0.053 | 0.0954503805726 | gnomAD-4.0.0 | 1.59247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88317E-05 | 0 | 0 | 0 | 0 |
| D/N | rs768380109  |
-0.397 | 0.939 | N | 0.398 | 0.228 | 0.190952846119 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/N | rs768380109 |
-0.397 | 0.939 | N | 0.398 | 0.228 | 0.190952846119 | gnomAD-4.0.0 | 6.8444E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99675E-07 | 0 | 0 |
| D/Y | rs768380109 |
-0.205 | 0.999 | N | 0.635 | 0.297 | 0.448099371145 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| D/Y | rs768380109 |
-0.205 | 0.999 | N | 0.635 | 0.297 | 0.448099371145 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 7.77001E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/Y | rs768380109 |
-0.205 | 0.999 | N | 0.635 | 0.297 | 0.448099371145 | gnomAD-4.0.0 | 1.61168E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.34156E-04 | None | 0 | 0 | 1.44131E-05 | 1.09835E-05 | 3.20277E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2318 | likely_benign | 0.2205 | benign | -0.314 | Destabilizing | 0.939 | D | 0.478 | neutral | N | 0.503482346 | None | None | N |
| D/C | 0.7993 | likely_pathogenic | 0.7881 | pathogenic | -0.142 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| D/E | 0.1756 | likely_benign | 0.1607 | benign | -0.265 | Destabilizing | 0.02 | N | 0.243 | neutral | N | 0.433043613 | None | None | N |
| D/F | 0.8522 | likely_pathogenic | 0.8455 | pathogenic | 0.053 | Stabilizing | 0.999 | D | 0.634 | neutral | None | None | None | None | N |
| D/G | 0.3476 | ambiguous | 0.3345 | benign | -0.556 | Destabilizing | 0.969 | D | 0.462 | neutral | N | 0.488027317 | None | None | N |
| D/H | 0.5547 | ambiguous | 0.5437 | ambiguous | 0.291 | Stabilizing | 0.998 | D | 0.497 | neutral | N | 0.501039473 | None | None | N |
| D/I | 0.5142 | ambiguous | 0.5176 | ambiguous | 0.291 | Stabilizing | 0.993 | D | 0.651 | neutral | None | None | None | None | N |
| D/K | 0.5657 | likely_pathogenic | 0.5783 | pathogenic | 0.312 | Stabilizing | 0.91 | D | 0.46 | neutral | None | None | None | None | N |
| D/L | 0.5594 | ambiguous | 0.5485 | ambiguous | 0.291 | Stabilizing | 0.986 | D | 0.639 | neutral | None | None | None | None | N |
| D/M | 0.7652 | likely_pathogenic | 0.7502 | pathogenic | 0.324 | Stabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| D/N | 0.159 | likely_benign | 0.1519 | benign | -0.257 | Destabilizing | 0.939 | D | 0.398 | neutral | N | 0.446588913 | None | None | N |
| D/P | 0.548 | ambiguous | 0.533 | ambiguous | 0.112 | Stabilizing | 0.993 | D | 0.502 | neutral | None | None | None | None | N |
| D/Q | 0.4995 | ambiguous | 0.4776 | ambiguous | -0.156 | Destabilizing | 0.973 | D | 0.442 | neutral | None | None | None | None | N |
| D/R | 0.6147 | likely_pathogenic | 0.6112 | pathogenic | 0.576 | Stabilizing | 0.986 | D | 0.581 | neutral | None | None | None | None | N |
| D/S | 0.1784 | likely_benign | 0.1715 | benign | -0.343 | Destabilizing | 0.953 | D | 0.381 | neutral | None | None | None | None | N |
| D/T | 0.3429 | ambiguous | 0.3337 | benign | -0.133 | Destabilizing | 0.986 | D | 0.458 | neutral | None | None | None | None | N |
| D/V | 0.3353 | likely_benign | 0.3317 | benign | 0.112 | Stabilizing | 0.991 | D | 0.639 | neutral | N | 0.454023501 | None | None | N |
| D/W | 0.9586 | likely_pathogenic | 0.9555 | pathogenic | 0.273 | Stabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| D/Y | 0.4326 | ambiguous | 0.4489 | ambiguous | 0.319 | Stabilizing | 0.999 | D | 0.635 | neutral | N | 0.469165241 | 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.