Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24571 | 73936;73937;73938 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| N2AB | 22930 | 69013;69014;69015 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| N2A | 22003 | 66232;66233;66234 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| N2B | 15506 | 46741;46742;46743 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| Novex-1 | 15631 | 47116;47117;47118 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| Novex-2 | 15698 | 47317;47318;47319 | chr2:178572421;178572420;178572419 | chr2:179437148;179437147;179437146 |
| 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 | rs752184535  |
-0.494 | None | N | 0.145 | 0.107 | 0.117506650769 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/A | rs752184535 |
-0.494 | None | N | 0.145 | 0.107 | 0.117506650769 | gnomAD-4.0.0 | 1.59322E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8628E-06 | 0 | 0 |
| T/I | None | None | 0.441 | N | 0.498 | 0.39 | 0.384919354899 | gnomAD-4.0.0 | 4.77992E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.58915E-06 | 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 | 0.0709 | likely_benign | 0.0569 | benign | -0.639 | Destabilizing | None | N | 0.145 | neutral | N | 0.475962963 | None | None | N |
| T/C | 0.4451 | ambiguous | 0.3842 | ambiguous | -0.28 | Destabilizing | 0.847 | D | 0.517 | neutral | None | None | None | None | N |
| T/D | 0.5888 | likely_pathogenic | 0.5042 | ambiguous | -0.221 | Destabilizing | 0.183 | N | 0.421 | neutral | None | None | None | None | N |
| T/E | 0.5294 | ambiguous | 0.4571 | ambiguous | -0.283 | Destabilizing | 0.427 | N | 0.429 | neutral | None | None | None | None | N |
| T/F | 0.4408 | ambiguous | 0.3729 | ambiguous | -1.022 | Destabilizing | 0.952 | D | 0.55 | neutral | None | None | None | None | N |
| T/G | 0.1892 | likely_benign | 0.1564 | benign | -0.809 | Destabilizing | 0.279 | N | 0.385 | neutral | None | None | None | None | N |
| T/H | 0.411 | ambiguous | 0.38 | ambiguous | -1.179 | Destabilizing | 0.958 | D | 0.523 | neutral | None | None | None | None | N |
| T/I | 0.2992 | likely_benign | 0.2464 | benign | -0.294 | Destabilizing | 0.441 | N | 0.498 | neutral | N | 0.48147455 | None | None | N |
| T/K | 0.4255 | ambiguous | 0.3995 | ambiguous | -0.557 | Destabilizing | 0.441 | N | 0.419 | neutral | N | 0.514422563 | None | None | N |
| T/L | 0.1417 | likely_benign | 0.1192 | benign | -0.294 | Destabilizing | 0.301 | N | 0.411 | neutral | None | None | None | None | N |
| T/M | 0.1235 | likely_benign | 0.112 | benign | 0.148 | Stabilizing | 0.958 | D | 0.519 | neutral | None | None | None | None | N |
| T/N | 0.1504 | likely_benign | 0.1364 | benign | -0.346 | Destabilizing | 0.183 | N | 0.364 | neutral | None | None | None | None | N |
| T/P | 0.1367 | likely_benign | 0.1056 | benign | -0.38 | Destabilizing | 0.255 | N | 0.495 | neutral | N | 0.470727356 | None | None | N |
| T/Q | 0.3319 | likely_benign | 0.3102 | benign | -0.652 | Destabilizing | 0.632 | D | 0.564 | neutral | None | None | None | None | N |
| T/R | 0.3801 | ambiguous | 0.3594 | ambiguous | -0.228 | Destabilizing | 0.678 | D | 0.512 | neutral | N | 0.517654869 | None | None | N |
| T/S | 0.1051 | likely_benign | 0.091 | benign | -0.571 | Destabilizing | None | N | 0.139 | neutral | N | 0.459259927 | None | None | N |
| T/V | 0.1782 | likely_benign | 0.1429 | benign | -0.38 | Destabilizing | 0.134 | N | 0.379 | neutral | None | None | None | None | N |
| T/W | 0.7665 | likely_pathogenic | 0.7281 | pathogenic | -0.955 | Destabilizing | 0.996 | D | 0.547 | neutral | None | None | None | None | N |
| T/Y | 0.4667 | ambiguous | 0.4176 | ambiguous | -0.707 | Destabilizing | 0.984 | D | 0.545 | 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.