Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24868 | 74827;74828;74829 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| N2AB | 23227 | 69904;69905;69906 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| N2A | 22300 | 67123;67124;67125 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| N2B | 15803 | 47632;47633;47634 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| Novex-1 | 15928 | 48007;48008;48009 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| Novex-2 | 15995 | 48208;48209;48210 | chr2:178571530;178571529;178571528 | chr2:179436257;179436256;179436255 |
| 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/K | None | None | 0.968 | N | 0.714 | 0.433 | 0.700192931172 | gnomAD-4.0.0 | 1.36884E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7992E-06 | 0 | 0 |
| I/L | None | None | 0.011 | N | 0.295 | 0.101 | 0.443388199986 | gnomAD-4.0.0 | 6.86029E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02008E-07 | 0 | 0 |
| I/R | None | None | 0.984 | N | 0.766 | 0.48 | 0.720578909528 | gnomAD-4.0.0 | 6.84422E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99601E-07 | 0 | 0 |
| I/V | rs72646898  |
-0.804 | 0.437 | N | 0.462 | 0.071 | None | gnomAD-2.1.1 | 2.36829E-04 | None | None | None | None | N | None | 2.48201E-04 | 1.13456E-04 | None | 0 | 0 | None | 0 | None | 0 | 4.40869E-04 | 0 |
| I/V | rs72646898 |
-0.804 | 0.437 | N | 0.462 | 0.071 | None | gnomAD-3.1.2 | 2.76669E-04 | None | None | None | None | N | None | 2.65534E-04 | 3.27525E-04 | 0 | 0 | 0 | None | 0 | 0 | 3.83617E-04 | 0 | 0 |
| I/V | rs72646898 |
-0.804 | 0.437 | N | 0.462 | 0.071 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| I/V | rs72646898 |
-0.804 | 0.437 | N | 0.462 | 0.071 | None | gnomAD-4.0.0 | 4.65958E-04 | None | None | None | None | N | None | 1.7337E-04 | 1.334E-04 | None | 0 | 0 | None | 0 | 0 | 6.02683E-04 | 0 | 3.2079E-04 |
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 | 0.798 | likely_pathogenic | 0.79 | pathogenic | -1.728 | Destabilizing | 0.825 | D | 0.575 | neutral | None | None | None | None | N |
| I/C | 0.8607 | likely_pathogenic | 0.8355 | pathogenic | -1.273 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| I/D | 0.9947 | likely_pathogenic | 0.9945 | pathogenic | -0.877 | Destabilizing | 0.988 | D | 0.721 | prob.delet. | None | None | None | None | N |
| I/E | 0.9825 | likely_pathogenic | 0.9824 | pathogenic | -0.741 | Destabilizing | 0.988 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/F | 0.2892 | likely_benign | 0.2847 | benign | -0.877 | Destabilizing | 0.976 | D | 0.501 | neutral | None | None | None | None | N |
| I/G | 0.9682 | likely_pathogenic | 0.9669 | pathogenic | -2.179 | Highly Destabilizing | 0.988 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/H | 0.9639 | likely_pathogenic | 0.9596 | pathogenic | -1.347 | Destabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| I/K | 0.9639 | likely_pathogenic | 0.9626 | pathogenic | -1.192 | Destabilizing | 0.968 | D | 0.714 | prob.delet. | N | 0.474762599 | None | None | N |
| I/L | 0.135 | likely_benign | 0.1421 | benign | -0.503 | Destabilizing | 0.011 | N | 0.295 | neutral | N | 0.402942497 | None | None | N |
| I/M | 0.1356 | likely_benign | 0.1408 | benign | -0.581 | Destabilizing | 0.968 | D | 0.529 | neutral | N | 0.511784903 | None | None | N |
| I/N | 0.9193 | likely_pathogenic | 0.9263 | pathogenic | -1.301 | Destabilizing | 0.988 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/P | 0.9922 | likely_pathogenic | 0.9923 | pathogenic | -0.883 | Destabilizing | 0.996 | D | 0.766 | deleterious | None | None | None | None | N |
| I/Q | 0.9473 | likely_pathogenic | 0.9449 | pathogenic | -1.231 | Destabilizing | 0.996 | D | 0.78 | deleterious | None | None | None | None | N |
| I/R | 0.9446 | likely_pathogenic | 0.9405 | pathogenic | -0.886 | Destabilizing | 0.984 | D | 0.766 | deleterious | N | 0.481092475 | None | None | N |
| I/S | 0.8727 | likely_pathogenic | 0.8746 | pathogenic | -2.083 | Highly Destabilizing | 0.851 | D | 0.599 | neutral | None | None | None | None | N |
| I/T | 0.8123 | likely_pathogenic | 0.8201 | pathogenic | -1.797 | Destabilizing | 0.103 | N | 0.456 | neutral | N | 0.461510798 | None | None | N |
| I/V | 0.1156 | likely_benign | 0.1116 | benign | -0.883 | Destabilizing | 0.437 | N | 0.462 | neutral | N | 0.452771098 | None | None | N |
| I/W | 0.9458 | likely_pathogenic | 0.9276 | pathogenic | -1.04 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| I/Y | 0.8029 | likely_pathogenic | 0.784 | pathogenic | -0.765 | Destabilizing | 0.988 | D | 0.669 | 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.