Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17161 | 51706;51707;51708 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| N2AB | 15520 | 46783;46784;46785 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| N2A | 14593 | 44002;44003;44004 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| N2B | 8096 | 24511;24512;24513 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| Novex-1 | 8221 | 24886;24887;24888 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| Novex-2 | 8288 | 25087;25088;25089 | chr2:178609942;178609941;178609940 | chr2:179474669;179474668;179474667 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.016 | N | 0.225 | 0.119 | 0.154104182512 | gnomAD-4.0.0 | 3.18655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86755E-05 | 0 |
| A/V | rs16866412  |
-0.538 | 0.98 | N | 0.628 | 0.305 | None | gnomAD-2.1.1 | 3.46646E-02 | None | None | None | None | N | None | 7.43836E-02 | 1.41108E-02 | None | 2.54122E-02 | 1.31989E-01 | None | 5.75401E-02 | None | 4.0432E-02 | 1.24279E-02 | 2.99916E-02 |
| A/V | rs16866412 |
-0.538 | 0.98 | N | 0.628 | 0.305 | None | gnomAD-3.1.2 | 3.83395E-02 | None | None | None | None | N | None | 7.35728E-02 | 2.85076E-02 | 9.86842E-03 | 2.42075E-02 | 1.32319E-01 | None | 4.22801E-02 | 2.8481E-02 | 1.14095E-02 | 5.45417E-02 | 3.73206E-02 |
| A/V | rs16866412 |
-0.538 | 0.98 | N | 0.628 | 0.305 | None | 1000 genomes | 7.26837E-02 | None | None | None | None | N | None | 8.7E-02 | 2.16E-02 | None | None | 1.558E-01 | 2.09E-02 | None | None | None | 5.73E-02 | None |
| A/V | rs16866412 |
-0.538 | 0.98 | N | 0.628 | 0.305 | None | gnomAD-4.0.0 | 2.26018E-02 | None | None | None | None | N | None | 7.33853E-02 | 1.85352E-02 | None | 2.52587E-02 | 1.35307E-01 | None | 4.07231E-02 | 3.95433E-02 | 1.10701E-02 | 5.75161E-02 | 3.04681E-02 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.485 | ambiguous | 0.4948 | ambiguous | -1.006 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| A/D | 0.6998 | likely_pathogenic | 0.704 | pathogenic | -2.0 | Highly Destabilizing | 0.919 | D | 0.659 | neutral | None | None | None | None | N |
| A/E | 0.472 | ambiguous | 0.4766 | ambiguous | -2.098 | Highly Destabilizing | 0.956 | D | 0.639 | neutral | N | 0.447349422 | None | None | N |
| A/F | 0.6006 | likely_pathogenic | 0.6389 | pathogenic | -1.375 | Destabilizing | 0.996 | D | 0.666 | neutral | None | None | None | None | N |
| A/G | 0.1741 | likely_benign | 0.1774 | benign | -1.054 | Destabilizing | 0.819 | D | 0.613 | neutral | N | 0.442810394 | None | None | N |
| A/H | 0.5771 | likely_pathogenic | 0.5995 | pathogenic | -1.074 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| A/I | 0.4861 | ambiguous | 0.5328 | ambiguous | -0.669 | Destabilizing | 0.988 | D | 0.65 | neutral | None | None | None | None | N |
| A/K | 0.3405 | ambiguous | 0.3576 | ambiguous | -1.149 | Destabilizing | 0.919 | D | 0.648 | neutral | None | None | None | None | N |
| A/L | 0.383 | ambiguous | 0.4025 | ambiguous | -0.669 | Destabilizing | 0.919 | D | 0.634 | neutral | None | None | None | None | N |
| A/M | 0.394 | ambiguous | 0.4186 | ambiguous | -0.418 | Destabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | N |
| A/N | 0.5071 | ambiguous | 0.5286 | ambiguous | -0.958 | Destabilizing | 0.919 | D | 0.66 | neutral | None | None | None | None | N |
| A/P | 0.6617 | likely_pathogenic | 0.5896 | pathogenic | -0.714 | Destabilizing | 0.984 | D | 0.651 | neutral | N | 0.44238632 | None | None | N |
| A/Q | 0.4114 | ambiguous | 0.4216 | ambiguous | -1.312 | Destabilizing | 0.988 | D | 0.639 | neutral | None | None | None | None | N |
| A/R | 0.308 | likely_benign | 0.3191 | benign | -0.612 | Destabilizing | 0.976 | D | 0.647 | neutral | None | None | None | None | N |
| A/S | 0.0982 | likely_benign | 0.1022 | benign | -1.107 | Destabilizing | 0.016 | N | 0.225 | neutral | N | 0.387164968 | None | None | N |
| A/T | 0.1653 | likely_benign | 0.1663 | benign | -1.148 | Destabilizing | 0.64 | D | 0.621 | neutral | N | 0.47730697 | None | None | N |
| A/V | 0.2444 | likely_benign | 0.2171 | benign | -0.714 | Destabilizing | 0.98 | D | 0.628 | neutral | N | 0.499415825 | None | None | N |
| A/W | 0.88 | likely_pathogenic | 0.8826 | pathogenic | -1.585 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| A/Y | 0.6921 | likely_pathogenic | 0.6941 | pathogenic | -1.225 | Destabilizing | 0.996 | D | 0.662 | neutral | 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.