Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19461 | 58606;58607;58608 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| N2AB | 17820 | 53683;53684;53685 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| N2A | 16893 | 50902;50903;50904 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| N2B | 10396 | 31411;31412;31413 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| Novex-1 | 10521 | 31786;31787;31788 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| Novex-2 | 10588 | 31987;31988;31989 | chr2:178594012;178594011;178594010 | chr2:179458739;179458738;179458737 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs368431326  |
-0.575 | 0.121 | N | 0.317 | 0.317 | 0.554116578535 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| V/L | rs368431326 |
-0.575 | 0.121 | N | 0.317 | 0.317 | 0.554116578535 | gnomAD-4.0.0 | 1.5917E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8591E-06 | 0 | 0 |
| V/M | rs368431326 |
-0.812 | 0.994 | N | 0.751 | 0.377 | 0.706693336582 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4075 | ambiguous | 0.4004 | ambiguous | -1.864 | Destabilizing | 0.989 | D | 0.653 | neutral | N | 0.448451074 | None | None | N |
| V/C | 0.9226 | likely_pathogenic | 0.9302 | pathogenic | -1.451 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| V/D | 0.9964 | likely_pathogenic | 0.9968 | pathogenic | -2.254 | Highly Destabilizing | 0.999 | D | 0.845 | deleterious | None | None | None | None | N |
| V/E | 0.9902 | likely_pathogenic | 0.9898 | pathogenic | -2.095 | Highly Destabilizing | 0.999 | D | 0.825 | deleterious | D | 0.530306127 | None | None | N |
| V/F | 0.8237 | likely_pathogenic | 0.8402 | pathogenic | -1.134 | Destabilizing | 0.995 | D | 0.802 | deleterious | None | None | None | None | N |
| V/G | 0.8288 | likely_pathogenic | 0.827 | pathogenic | -2.345 | Highly Destabilizing | 0.999 | D | 0.847 | deleterious | N | 0.497958731 | None | None | N |
| V/H | 0.9979 | likely_pathogenic | 0.998 | pathogenic | -2.1 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| V/I | 0.0986 | likely_benign | 0.1128 | benign | -0.559 | Destabilizing | 0.437 | N | 0.278 | neutral | None | None | None | None | N |
| V/K | 0.9953 | likely_pathogenic | 0.995 | pathogenic | -1.582 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| V/L | 0.3028 | likely_benign | 0.3176 | benign | -0.559 | Destabilizing | 0.121 | N | 0.317 | neutral | N | 0.484425809 | None | None | N |
| V/M | 0.5076 | ambiguous | 0.5227 | ambiguous | -0.617 | Destabilizing | 0.994 | D | 0.751 | deleterious | N | 0.495819137 | None | None | N |
| V/N | 0.9896 | likely_pathogenic | 0.9909 | pathogenic | -1.722 | Destabilizing | 0.999 | D | 0.849 | deleterious | None | None | None | None | N |
| V/P | 0.9935 | likely_pathogenic | 0.9931 | pathogenic | -0.964 | Destabilizing | 0.999 | D | 0.812 | deleterious | None | None | None | None | N |
| V/Q | 0.9889 | likely_pathogenic | 0.9887 | pathogenic | -1.655 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| V/R | 0.9887 | likely_pathogenic | 0.9881 | pathogenic | -1.339 | Destabilizing | 0.999 | D | 0.847 | deleterious | None | None | None | None | N |
| V/S | 0.8856 | likely_pathogenic | 0.893 | pathogenic | -2.322 | Highly Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| V/T | 0.6934 | likely_pathogenic | 0.6966 | pathogenic | -2.032 | Highly Destabilizing | 0.992 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/W | 0.9975 | likely_pathogenic | 0.9977 | pathogenic | -1.601 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| V/Y | 0.9916 | likely_pathogenic | 0.9924 | pathogenic | -1.218 | Destabilizing | 0.999 | D | 0.785 | 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.