Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21780 | 65563;65564;65565 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| N2AB | 20139 | 60640;60641;60642 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| N2A | 19212 | 57859;57860;57861 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| N2B | 12715 | 38368;38369;38370 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| Novex-1 | 12840 | 38743;38744;38745 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| Novex-2 | 12907 | 38944;38945;38946 | chr2:178583844;178583843;178583842 | chr2:179448571;179448570;179448569 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs745681257  |
-1.077 | 0.999 | N | 0.784 | 0.399 | 0.604945591675 | gnomAD-2.1.1 | 1.47E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.24E-05 | 0 |
| R/C | rs745681257 |
-1.077 | 0.999 | N | 0.784 | 0.399 | 0.604945591675 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs745681257 |
-1.077 | 0.999 | N | 0.784 | 0.399 | 0.604945591675 | gnomAD-4.0.0 | 1.30546E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69868E-05 | 1.11044E-05 | 0 |
| R/H | rs779044914 |
-1.842 | 1.0 | N | 0.572 | 0.309 | 0.299427821978 | gnomAD-2.1.1 | 1.66E-05 | None | None | None | None | N | None | 0 | 2.97E-05 | None | 0 | 5.77E-05 | None | 3.41E-05 | None | 0 | 9.24E-06 | 0 |
| R/H | rs779044914 |
-1.842 | 1.0 | N | 0.572 | 0.309 | 0.299427821978 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs779044914 |
-1.842 | 1.0 | N | 0.572 | 0.309 | 0.299427821978 | gnomAD-4.0.0 | 1.05671E-05 | None | None | None | None | N | None | 1.33704E-05 | 3.36101E-05 | None | 0 | 2.24699E-05 | None | 0 | 0 | 6.79439E-06 | 5.55235E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3534 | ambiguous | 0.277 | benign | -0.423 | Destabilizing | 0.033 | N | 0.353 | neutral | None | None | None | None | N |
| R/C | 0.1795 | likely_benign | 0.1368 | benign | -0.512 | Destabilizing | 0.999 | D | 0.784 | deleterious | N | 0.474762599 | None | None | N |
| R/D | 0.799 | likely_pathogenic | 0.715 | pathogenic | -0.397 | Destabilizing | 0.987 | D | 0.747 | deleterious | None | None | None | None | N |
| R/E | 0.4209 | ambiguous | 0.3509 | ambiguous | -0.231 | Destabilizing | 0.916 | D | 0.529 | neutral | None | None | None | None | N |
| R/F | 0.6243 | likely_pathogenic | 0.5293 | ambiguous | -0.121 | Destabilizing | 0.987 | D | 0.802 | deleterious | None | None | None | None | N |
| R/G | 0.3298 | likely_benign | 0.25 | benign | -0.748 | Destabilizing | 0.913 | D | 0.606 | neutral | N | 0.495988731 | None | None | N |
| R/H | 0.1237 | likely_benign | 0.102 | benign | -1.331 | Destabilizing | 1.0 | D | 0.572 | neutral | N | 0.47012779 | None | None | N |
| R/I | 0.3688 | ambiguous | 0.3011 | benign | 0.453 | Stabilizing | 0.975 | D | 0.794 | deleterious | None | None | None | None | N |
| R/K | 0.0928 | likely_benign | 0.0828 | benign | -0.363 | Destabilizing | 0.818 | D | 0.529 | neutral | None | None | None | None | N |
| R/L | 0.2721 | likely_benign | 0.2244 | benign | 0.453 | Stabilizing | 0.913 | D | 0.632 | neutral | N | 0.513497056 | None | None | N |
| R/M | 0.3691 | ambiguous | 0.3014 | benign | -0.202 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/N | 0.6762 | likely_pathogenic | 0.5732 | pathogenic | -0.331 | Destabilizing | 0.987 | D | 0.547 | neutral | None | None | None | None | N |
| R/P | 0.2732 | likely_benign | 0.2083 | benign | 0.182 | Stabilizing | 0.993 | D | 0.773 | deleterious | N | 0.413153917 | None | None | N |
| R/Q | 0.108 | likely_benign | 0.0935 | benign | -0.246 | Destabilizing | 0.987 | D | 0.541 | neutral | None | None | None | None | N |
| R/S | 0.5161 | ambiguous | 0.4173 | ambiguous | -0.753 | Destabilizing | 0.913 | D | 0.601 | neutral | N | 0.51567057 | None | None | N |
| R/T | 0.3352 | likely_benign | 0.2624 | benign | -0.388 | Destabilizing | 0.916 | D | 0.637 | neutral | None | None | None | None | N |
| R/V | 0.3983 | ambiguous | 0.3359 | benign | 0.182 | Stabilizing | 0.95 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/W | 0.2639 | likely_benign | 0.2199 | benign | 0.006 | Stabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| R/Y | 0.5048 | ambiguous | 0.4143 | ambiguous | 0.309 | Stabilizing | 0.996 | D | 0.779 | deleterious | 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.