Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23992 | 72199;72200;72201 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| N2AB | 22351 | 67276;67277;67278 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| N2A | 21424 | 64495;64496;64497 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| N2B | 14927 | 45004;45005;45006 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| Novex-1 | 15052 | 45379;45380;45381 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| Novex-2 | 15119 | 45580;45581;45582 | chr2:178574158;178574157;178574156 | chr2:179438885;179438884;179438883 |
| 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/A | rs767782229  |
-0.063 | 0.939 | N | 0.656 | 0.31 | 0.367229591828 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/A | rs767782229 |
-0.063 | 0.939 | N | 0.656 | 0.31 | 0.367229591828 | gnomAD-4.0.0 | 1.36858E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7991E-06 | 0 | 0 |
| D/Y | rs775852603 |
-0.167 | 0.999 | N | 0.747 | 0.312 | 0.602559457607 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/Y | rs775852603 |
-0.167 | 0.999 | N | 0.747 | 0.312 | 0.602559457607 | gnomAD-4.0.0 | 1.36858E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7991E-06 | 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 | 0.3035 | likely_benign | 0.3194 | benign | -0.091 | Destabilizing | 0.939 | D | 0.656 | neutral | N | 0.502530701 | None | None | N |
| D/C | 0.8099 | likely_pathogenic | 0.8022 | pathogenic | 0.219 | Stabilizing | 0.999 | D | 0.803 | deleterious | None | None | None | None | N |
| D/E | 0.2578 | likely_benign | 0.2506 | benign | -0.207 | Destabilizing | 0.939 | D | 0.506 | neutral | N | 0.475056099 | None | None | N |
| D/F | 0.6636 | likely_pathogenic | 0.6923 | pathogenic | -0.293 | Destabilizing | 0.999 | D | 0.747 | deleterious | None | None | None | None | N |
| D/G | 0.1215 | likely_benign | 0.1209 | benign | -0.257 | Destabilizing | 0.046 | N | 0.426 | neutral | N | 0.376539756 | None | None | N |
| D/H | 0.4299 | ambiguous | 0.4418 | ambiguous | -0.184 | Destabilizing | 0.998 | D | 0.649 | neutral | D | 0.523367333 | None | None | N |
| D/I | 0.6926 | likely_pathogenic | 0.7199 | pathogenic | 0.285 | Stabilizing | 0.998 | D | 0.75 | deleterious | None | None | None | None | N |
| D/K | 0.5943 | likely_pathogenic | 0.5825 | pathogenic | 0.321 | Stabilizing | 0.986 | D | 0.622 | neutral | None | None | None | None | N |
| D/L | 0.5758 | likely_pathogenic | 0.5869 | pathogenic | 0.285 | Stabilizing | 0.993 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/M | 0.7584 | likely_pathogenic | 0.7624 | pathogenic | 0.425 | Stabilizing | 0.999 | D | 0.781 | deleterious | None | None | None | None | N |
| D/N | 0.0889 | likely_benign | 0.0954 | benign | 0.303 | Stabilizing | 0.1 | N | 0.401 | neutral | N | 0.457027698 | None | None | N |
| D/P | 0.9472 | likely_pathogenic | 0.9543 | pathogenic | 0.182 | Stabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | N |
| D/Q | 0.5703 | likely_pathogenic | 0.5576 | ambiguous | 0.29 | Stabilizing | 0.993 | D | 0.646 | neutral | None | None | None | None | N |
| D/R | 0.6505 | likely_pathogenic | 0.6521 | pathogenic | 0.413 | Stabilizing | 0.986 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/S | 0.2087 | likely_benign | 0.209 | benign | 0.139 | Stabilizing | 0.91 | D | 0.581 | neutral | None | None | None | None | N |
| D/T | 0.4429 | ambiguous | 0.4479 | ambiguous | 0.252 | Stabilizing | 0.986 | D | 0.627 | neutral | None | None | None | None | N |
| D/V | 0.4893 | ambiguous | 0.5189 | ambiguous | 0.182 | Stabilizing | 0.991 | D | 0.739 | prob.delet. | N | 0.493956491 | None | None | N |
| D/W | 0.9175 | likely_pathogenic | 0.9257 | pathogenic | -0.276 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | None | N |
| D/Y | 0.2469 | likely_benign | 0.2677 | benign | -0.084 | Destabilizing | 0.999 | D | 0.747 | deleterious | N | 0.51913495 | 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.