Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22748 | 68467;68468;68469 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| N2AB | 21107 | 63544;63545;63546 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| N2A | 20180 | 60763;60764;60765 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| N2B | 13683 | 41272;41273;41274 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| Novex-1 | 13808 | 41647;41648;41649 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| Novex-2 | 13875 | 41848;41849;41850 | chr2:178578698;178578697;178578696 | chr2:179443425;179443424;179443423 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs780062324  |
-0.81 | 0.961 | N | 0.606 | 0.318 | 0.491044626064 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.59E-05 | 0 |
| P/L | rs780062324 |
-0.81 | 0.961 | N | 0.606 | 0.318 | 0.491044626064 | gnomAD-4.0.0 | 2.12469E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87448E-05 | 0 | 2.61045E-05 | 1.16978E-05 | 0 |
| P/R | None | None | 0.994 | N | 0.635 | 0.358 | 0.375326005269 | gnomAD-4.0.0 | 6.85384E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00155E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0663 | likely_benign | 0.0623 | benign | -1.628 | Destabilizing | 0.122 | N | 0.331 | neutral | N | 0.401654418 | None | None | N |
| P/C | 0.3905 | ambiguous | 0.3506 | ambiguous | -1.105 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/D | 0.3917 | ambiguous | 0.3586 | ambiguous | -1.726 | Destabilizing | 0.996 | D | 0.542 | neutral | None | None | None | None | N |
| P/E | 0.2479 | likely_benign | 0.2221 | benign | -1.709 | Destabilizing | 0.985 | D | 0.519 | neutral | None | None | None | None | N |
| P/F | 0.3413 | ambiguous | 0.2961 | benign | -1.214 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| P/G | 0.2327 | likely_benign | 0.2006 | benign | -1.966 | Destabilizing | 0.942 | D | 0.587 | neutral | None | None | None | None | N |
| P/H | 0.196 | likely_benign | 0.1715 | benign | -1.624 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | N |
| P/I | 0.2168 | likely_benign | 0.2065 | benign | -0.784 | Destabilizing | 0.991 | D | 0.649 | neutral | None | None | None | None | N |
| P/K | 0.2925 | likely_benign | 0.2544 | benign | -1.427 | Destabilizing | 0.97 | D | 0.519 | neutral | None | None | None | None | N |
| P/L | 0.0887 | likely_benign | 0.0782 | benign | -0.784 | Destabilizing | 0.961 | D | 0.606 | neutral | N | 0.422299049 | None | None | N |
| P/M | 0.2062 | likely_benign | 0.1884 | benign | -0.626 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/N | 0.2787 | likely_benign | 0.2437 | benign | -1.228 | Destabilizing | 0.996 | D | 0.63 | neutral | None | None | None | None | N |
| P/Q | 0.1452 | likely_benign | 0.1239 | benign | -1.384 | Destabilizing | 0.998 | D | 0.574 | neutral | N | 0.425664641 | None | None | N |
| P/R | 0.2287 | likely_benign | 0.1968 | benign | -0.945 | Destabilizing | 0.994 | D | 0.635 | neutral | N | 0.437265715 | None | None | N |
| P/S | 0.0942 | likely_benign | 0.0846 | benign | -1.717 | Destabilizing | 0.925 | D | 0.531 | neutral | N | 0.354572547 | None | None | N |
| P/T | 0.0979 | likely_benign | 0.0897 | benign | -1.596 | Destabilizing | 0.248 | N | 0.363 | neutral | N | 0.367771131 | None | None | N |
| P/V | 0.1519 | likely_benign | 0.1429 | benign | -1.032 | Destabilizing | 0.97 | D | 0.588 | neutral | None | None | None | None | N |
| P/W | 0.607 | likely_pathogenic | 0.5532 | ambiguous | -1.459 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| P/Y | 0.3496 | ambiguous | 0.3068 | benign | -1.171 | Destabilizing | 0.999 | D | 0.711 | 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.