Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33451 | 100576;100577;100578 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| N2AB | 31810 | 95653;95654;95655 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| N2A | 30883 | 92872;92873;92874 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| N2B | 24386 | 73381;73382;73383 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| Novex-1 | 24511 | 73756;73757;73758 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| Novex-2 | 24578 | 73957;73958;73959 | chr2:178536396;178536395;178536394 | chr2:179401123;179401122;179401121 |
| 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/A | rs1467511236  |
-1.143 | 0.911 | N | 0.413 | 0.092 | 0.515430650102 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| V/L | rs2154137428 |
None | 0.977 | N | 0.464 | 0.203 | 0.498323335527 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| V/L | rs2154137428 |
None | 0.977 | N | 0.464 | 0.203 | 0.498323335527 | gnomAD-4.0.0 | 6.56564E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.40136E-03 | 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 | 0.217 | likely_benign | 0.3238 | benign | -1.172 | Destabilizing | 0.911 | D | 0.413 | neutral | N | 0.441172811 | None | None | I |
| V/C | 0.7231 | likely_pathogenic | 0.7994 | pathogenic | -0.709 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | I |
| V/D | 0.4922 | ambiguous | 0.7269 | pathogenic | -1.014 | Destabilizing | 0.961 | D | 0.587 | neutral | N | 0.469418205 | None | None | I |
| V/E | 0.3562 | ambiguous | 0.5708 | pathogenic | -0.942 | Destabilizing | 0.985 | D | 0.561 | neutral | None | None | None | None | I |
| V/F | 0.2256 | likely_benign | 0.3299 | benign | -0.706 | Destabilizing | 0.999 | D | 0.64 | neutral | N | 0.466185899 | None | None | I |
| V/G | 0.3277 | likely_benign | 0.4804 | ambiguous | -1.533 | Destabilizing | 0.98 | D | 0.558 | neutral | N | 0.476882895 | None | None | I |
| V/H | 0.5769 | likely_pathogenic | 0.7534 | pathogenic | -0.968 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| V/I | 0.097 | likely_benign | 0.0954 | benign | -0.261 | Destabilizing | 0.99 | D | 0.437 | neutral | N | 0.451005803 | None | None | I |
| V/K | 0.4387 | ambiguous | 0.6633 | pathogenic | -0.955 | Destabilizing | 0.985 | D | 0.56 | neutral | None | None | None | None | I |
| V/L | 0.274 | likely_benign | 0.3368 | benign | -0.261 | Destabilizing | 0.977 | D | 0.464 | neutral | N | 0.47291987 | None | None | I |
| V/M | 0.1992 | likely_benign | 0.2408 | benign | -0.273 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | I |
| V/N | 0.2782 | likely_benign | 0.4396 | ambiguous | -0.97 | Destabilizing | 0.469 | N | 0.409 | neutral | None | None | None | None | I |
| V/P | 0.9425 | likely_pathogenic | 0.9767 | pathogenic | -0.53 | Destabilizing | 0.998 | D | 0.673 | neutral | None | None | None | None | I |
| V/Q | 0.3612 | ambiguous | 0.5318 | ambiguous | -1.011 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | I |
| V/R | 0.3476 | ambiguous | 0.5779 | pathogenic | -0.561 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/S | 0.1957 | likely_benign | 0.317 | benign | -1.508 | Destabilizing | 0.719 | D | 0.287 | neutral | None | None | None | None | I |
| V/T | 0.1745 | likely_benign | 0.2575 | benign | -1.313 | Destabilizing | 0.971 | D | 0.395 | neutral | None | None | None | None | I |
| V/W | 0.8953 | likely_pathogenic | 0.9472 | pathogenic | -1.001 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| V/Y | 0.5719 | likely_pathogenic | 0.7315 | pathogenic | -0.623 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | I |
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.