Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15163 | 45712;45713;45714 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| N2AB | 13522 | 40789;40790;40791 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| N2A | 12595 | 38008;38009;38010 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| N2B | 6098 | 18517;18518;18519 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| Novex-1 | 6223 | 18892;18893;18894 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| Novex-2 | 6290 | 19093;19094;19095 | chr2:178621231;178621230;178621229 | chr2:179485958;179485957;179485956 |
| 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 | rs755689835  |
0.124 | 0.046 | N | 0.325 | 0.05 | 0.170165803431 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs755689835 |
0.124 | 0.046 | N | 0.325 | 0.05 | 0.170165803431 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44949E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs755689835 |
0.124 | 0.046 | N | 0.325 | 0.05 | 0.170165803431 | gnomAD-4.0.0 | 1.28357E-05 | None | None | None | None | N | None | 1.69469E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs2058223645 |
None | 0.322 | N | 0.327 | 0.248 | 0.227260227426 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs2058223645 |
None | 0.322 | N | 0.327 | 0.248 | 0.227260227426 | gnomAD-4.0.0 | 6.58597E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47323E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1856 | likely_benign | 0.1567 | benign | 0.068 | Stabilizing | 0.939 | D | 0.372 | neutral | N | 0.443527968 | None | None | N |
| D/C | 0.7136 | likely_pathogenic | 0.6216 | pathogenic | -0.2 | Destabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | N |
| D/E | 0.1391 | likely_benign | 0.1097 | benign | -0.424 | Destabilizing | 0.046 | N | 0.325 | neutral | N | 0.448207133 | None | None | N |
| D/F | 0.6255 | likely_pathogenic | 0.5626 | ambiguous | -0.075 | Destabilizing | 0.999 | D | 0.545 | neutral | None | None | None | None | N |
| D/G | 0.1574 | likely_benign | 0.1346 | benign | -0.013 | Destabilizing | 0.939 | D | 0.434 | neutral | N | 0.440309261 | None | None | N |
| D/H | 0.3538 | ambiguous | 0.2879 | benign | 0.581 | Stabilizing | 0.998 | D | 0.429 | neutral | N | 0.478503229 | None | None | N |
| D/I | 0.3563 | ambiguous | 0.3013 | benign | 0.213 | Stabilizing | 0.993 | D | 0.567 | neutral | None | None | None | None | N |
| D/K | 0.3465 | ambiguous | 0.2582 | benign | 0.396 | Stabilizing | 0.91 | D | 0.4 | neutral | None | None | None | None | N |
| D/L | 0.3855 | ambiguous | 0.3229 | benign | 0.213 | Stabilizing | 0.986 | D | 0.569 | neutral | None | None | None | None | N |
| D/M | 0.5969 | likely_pathogenic | 0.5152 | ambiguous | -0.016 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| D/N | 0.0982 | likely_benign | 0.0889 | benign | 0.185 | Stabilizing | 0.322 | N | 0.327 | neutral | N | 0.439306934 | None | None | N |
| D/P | 0.533 | ambiguous | 0.4287 | ambiguous | 0.182 | Stabilizing | 0.993 | D | 0.432 | neutral | None | None | None | None | N |
| D/Q | 0.332 | likely_benign | 0.2611 | benign | 0.172 | Stabilizing | 0.973 | D | 0.475 | neutral | None | None | None | None | N |
| D/R | 0.4299 | ambiguous | 0.3503 | ambiguous | 0.603 | Stabilizing | 0.986 | D | 0.484 | neutral | None | None | None | None | N |
| D/S | 0.1204 | likely_benign | 0.0986 | benign | 0.096 | Stabilizing | 0.953 | D | 0.423 | neutral | None | None | None | None | N |
| D/T | 0.2521 | likely_benign | 0.2047 | benign | 0.17 | Stabilizing | 0.986 | D | 0.395 | neutral | None | None | None | None | N |
| D/V | 0.2263 | likely_benign | 0.1945 | benign | 0.182 | Stabilizing | 0.991 | D | 0.568 | neutral | N | 0.510412798 | None | None | N |
| D/W | 0.8893 | likely_pathogenic | 0.8458 | pathogenic | -0.066 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| D/Y | 0.3021 | likely_benign | 0.2785 | benign | 0.14 | Stabilizing | 0.999 | D | 0.546 | neutral | D | 0.621422585 | 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.