Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19538 | 58837;58838;58839 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| N2AB | 17897 | 53914;53915;53916 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| N2A | 16970 | 51133;51134;51135 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| N2B | 10473 | 31642;31643;31644 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| Novex-1 | 10598 | 32017;32018;32019 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| Novex-2 | 10665 | 32218;32219;32220 | chr2:178593688;178593687;178593686 | chr2:179458415;179458414;179458413 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs200017524  |
-0.811 | 0.9 | N | 0.46 | 0.249 | None | gnomAD-2.1.1 | 4.54308E-04 | None | None | None | None | N | None | 4.46465E-03 | 3.4029E-04 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 1.40687E-04 |
| T/A | rs200017524 |
-0.811 | 0.9 | N | 0.46 | 0.249 | None | gnomAD-3.1.2 | 1.40725E-03 | None | None | None | None | N | None | 4.63499E-03 | 6.55136E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 3.83142E-03 |
| T/A | rs200017524 |
-0.811 | 0.9 | N | 0.46 | 0.249 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 4.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs200017524 |
-0.811 | 0.9 | N | 0.46 | 0.249 | None | gnomAD-4.0.0 | 2.61564E-04 | None | None | None | None | N | None | 4.69296E-03 | 4.16945E-04 | None | 6.7595E-05 | 0 | None | 0 | 1.6518E-04 | 1.52593E-05 | 0 | 3.84234E-04 |
| T/I | rs370686112 |
None | 0.997 | N | 0.722 | 0.433 | 0.565649094883 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| T/I | rs370686112 |
None | 0.997 | N | 0.722 | 0.433 | 0.565649094883 | gnomAD-4.0.0 | 6.57877E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.42507E-05 | 0 | 0 | 0 | 0 |
| T/K | rs370686112 |
-0.374 | 0.994 | N | 0.691 | 0.368 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 3.72055E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/K | rs370686112 |
-0.374 | 0.994 | N | 0.691 | 0.368 | None | gnomAD-3.1.2 | 1.0526E-04 | None | None | None | None | N | None | 3.86436E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs370686112 |
-0.374 | 0.994 | N | 0.691 | 0.368 | None | gnomAD-4.0.0 | 2.54157E-05 | None | None | None | None | N | None | 5.47689E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0996 | likely_benign | 0.0999 | benign | -0.876 | Destabilizing | 0.9 | D | 0.46 | neutral | N | 0.506437798 | None | None | N |
| T/C | 0.4143 | ambiguous | 0.4296 | ambiguous | -0.444 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| T/D | 0.5164 | ambiguous | 0.4757 | ambiguous | 0.059 | Stabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/E | 0.3771 | ambiguous | 0.3492 | ambiguous | 0.093 | Stabilizing | 0.995 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/F | 0.2409 | likely_benign | 0.2457 | benign | -0.867 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | N |
| T/G | 0.2931 | likely_benign | 0.2835 | benign | -1.163 | Destabilizing | 0.983 | D | 0.567 | neutral | None | None | None | None | N |
| T/H | 0.275 | likely_benign | 0.2623 | benign | -1.343 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| T/I | 0.1994 | likely_benign | 0.2088 | benign | -0.195 | Destabilizing | 0.997 | D | 0.722 | prob.delet. | N | 0.477626663 | None | None | N |
| T/K | 0.263 | likely_benign | 0.2416 | benign | -0.593 | Destabilizing | 0.994 | D | 0.691 | prob.neutral | N | 0.485062448 | None | None | N |
| T/L | 0.1416 | likely_benign | 0.1385 | benign | -0.195 | Destabilizing | 0.992 | D | 0.551 | neutral | None | None | None | None | N |
| T/M | 0.1046 | likely_benign | 0.1068 | benign | -0.044 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/N | 0.1636 | likely_benign | 0.156 | benign | -0.602 | Destabilizing | 0.995 | D | 0.634 | neutral | None | None | None | None | N |
| T/P | 0.6663 | likely_pathogenic | 0.6054 | pathogenic | -0.389 | Destabilizing | 0.997 | D | 0.723 | prob.delet. | D | 0.522388686 | None | None | N |
| T/Q | 0.2513 | likely_benign | 0.2372 | benign | -0.658 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | None | N |
| T/R | 0.2147 | likely_benign | 0.1979 | benign | -0.453 | Destabilizing | 0.997 | D | 0.729 | prob.delet. | N | 0.474594739 | None | None | N |
| T/S | 0.1032 | likely_benign | 0.1 | benign | -0.932 | Destabilizing | 0.63 | D | 0.293 | neutral | N | 0.406713521 | None | None | N |
| T/V | 0.1498 | likely_benign | 0.1536 | benign | -0.389 | Destabilizing | 0.992 | D | 0.528 | neutral | None | None | None | None | N |
| T/W | 0.6347 | likely_pathogenic | 0.6416 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/Y | 0.2838 | likely_benign | 0.2922 | benign | -0.58 | Destabilizing | 0.999 | D | 0.759 | 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.