Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32000 | 96223;96224;96225 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| N2AB | 30359 | 91300;91301;91302 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| N2A | 29432 | 88519;88520;88521 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| N2B | 22935 | 69028;69029;69030 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| Novex-1 | 23060 | 69403;69404;69405 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| Novex-2 | 23127 | 69604;69605;69606 | chr2:178544231;178544230;178544229 | chr2:179408958;179408957;179408956 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.001 | N | 0.308 | 0.086 | 0.236278675362 | gnomAD-4.0.0 | 6.8439E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65695E-05 |
| I/T | rs772265662  |
-2.224 | None | N | 0.313 | 0.111 | 0.134241683229 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.78E-05 | 0 |
| I/T | rs772265662 |
-2.224 | None | N | 0.313 | 0.111 | 0.134241683229 | gnomAD-4.0.0 | 8.8972E-06 | None | None | None | None | N | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 9.89744E-06 | 0 | 1.65689E-05 |
| I/V | rs769971164 |
None | None | N | 0.141 | 0.091 | 0.308904156042 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs769971164 |
None | None | N | 0.141 | 0.091 | 0.308904156042 | gnomAD-4.0.0 | 1.17767E-05 | None | None | None | None | N | None | 1.33469E-05 | 0 | None | 0 | 2.22816E-05 | None | 0 | 1.64582E-04 | 1.27177E-05 | 0 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.0741 | likely_benign | 0.0682 | benign | -1.72 | Destabilizing | 0.001 | N | 0.472 | neutral | None | None | None | None | N |
| I/C | 0.2821 | likely_benign | 0.2776 | benign | -1.165 | Destabilizing | 0.131 | N | 0.617 | neutral | None | None | None | None | N |
| I/D | 0.2777 | likely_benign | 0.2569 | benign | -0.701 | Destabilizing | 0.009 | N | 0.645 | neutral | None | None | None | None | N |
| I/E | 0.2555 | likely_benign | 0.2378 | benign | -0.606 | Destabilizing | 0.009 | N | 0.667 | prob.neutral | None | None | None | None | N |
| I/F | 0.1255 | likely_benign | 0.1226 | benign | -1.021 | Destabilizing | 0.016 | N | 0.543 | neutral | N | 0.474418593 | None | None | N |
| I/G | 0.1912 | likely_benign | 0.1812 | benign | -2.133 | Highly Destabilizing | 0.002 | N | 0.709 | prob.delet. | None | None | None | None | N |
| I/H | 0.2423 | likely_benign | 0.2265 | benign | -1.307 | Destabilizing | 0.314 | N | 0.659 | prob.neutral | None | None | None | None | N |
| I/K | 0.1873 | likely_benign | 0.1804 | benign | -1.006 | Destabilizing | 0.009 | N | 0.671 | prob.neutral | None | None | None | None | N |
| I/L | 0.0787 | likely_benign | 0.0817 | benign | -0.616 | Destabilizing | 0.001 | N | 0.308 | neutral | N | 0.408673604 | None | None | N |
| I/M | 0.0719 | likely_benign | 0.0716 | benign | -0.615 | Destabilizing | 0.053 | N | 0.539 | neutral | N | 0.466953903 | None | None | N |
| I/N | 0.099 | likely_benign | 0.0915 | benign | -0.998 | Destabilizing | 0.007 | N | 0.615 | neutral | N | 0.485982381 | None | None | N |
| I/P | 0.1881 | likely_benign | 0.1665 | benign | -0.954 | Destabilizing | 0.017 | N | 0.621 | neutral | None | None | None | None | N |
| I/Q | 0.2042 | likely_benign | 0.1894 | benign | -1.004 | Destabilizing | 0.041 | N | 0.628 | neutral | None | None | None | None | N |
| I/R | 0.159 | likely_benign | 0.145 | benign | -0.641 | Destabilizing | 0.021 | N | 0.629 | neutral | None | None | None | None | N |
| I/S | 0.0792 | likely_benign | 0.0691 | benign | -1.782 | Destabilizing | None | N | 0.379 | neutral | N | 0.325596434 | None | None | N |
| I/T | 0.0582 | likely_benign | 0.0539 | benign | -1.541 | Destabilizing | None | N | 0.313 | neutral | N | 0.373715668 | None | None | N |
| I/V | 0.0597 | likely_benign | 0.0611 | benign | -0.954 | Destabilizing | None | N | 0.141 | neutral | N | 0.404150432 | None | None | N |
| I/W | 0.5971 | likely_pathogenic | 0.5589 | ambiguous | -1.129 | Destabilizing | 0.633 | D | 0.653 | prob.neutral | None | None | None | None | N |
| I/Y | 0.3296 | likely_benign | 0.3112 | benign | -0.863 | Destabilizing | 0.041 | N | 0.716 | 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.