Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33452 | 100579;100580;100581 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| N2AB | 31811 | 95656;95657;95658 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| N2A | 30884 | 92875;92876;92877 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| N2B | 24387 | 73384;73385;73386 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| Novex-1 | 24512 | 73759;73760;73761 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| Novex-2 | 24579 | 73960;73961;73962 | chr2:178536393;178536392;178536391 | chr2:179401120;179401119;179401118 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/S | rs1450640139  |
-0.959 | 0.549 | N | 0.548 | 0.29 | 0.63141776442 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| F/S | rs1450640139 |
-0.959 | 0.549 | N | 0.548 | 0.29 | 0.63141776442 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/S | rs1450640139 |
-0.959 | 0.549 | N | 0.548 | 0.29 | 0.63141776442 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46994E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8021 | likely_pathogenic | 0.8051 | pathogenic | -2.185 | Highly Destabilizing | 0.617 | D | 0.511 | neutral | None | None | None | None | I |
| F/C | 0.3639 | ambiguous | 0.3409 | ambiguous | -1.688 | Destabilizing | 0.99 | D | 0.513 | neutral | N | 0.446024058 | None | None | I |
| F/D | 0.9468 | likely_pathogenic | 0.9534 | pathogenic | -1.861 | Destabilizing | 0.92 | D | 0.549 | neutral | None | None | None | None | I |
| F/E | 0.9476 | likely_pathogenic | 0.9603 | pathogenic | -1.681 | Destabilizing | 0.766 | D | 0.565 | neutral | None | None | None | None | I |
| F/G | 0.9325 | likely_pathogenic | 0.9393 | pathogenic | -2.575 | Highly Destabilizing | 0.766 | D | 0.567 | neutral | None | None | None | None | I |
| F/H | 0.5664 | likely_pathogenic | 0.5441 | ambiguous | -0.96 | Destabilizing | 0.85 | D | 0.551 | neutral | None | None | None | None | I |
| F/I | 0.4279 | ambiguous | 0.4368 | ambiguous | -0.953 | Destabilizing | 0.549 | D | 0.45 | neutral | N | 0.484118299 | None | None | I |
| F/K | 0.9186 | likely_pathogenic | 0.9438 | pathogenic | -1.943 | Destabilizing | 0.85 | D | 0.564 | neutral | None | None | None | None | I |
| F/L | 0.897 | likely_pathogenic | 0.8992 | pathogenic | -0.953 | Destabilizing | 0.201 | N | 0.471 | neutral | N | 0.46926349 | None | None | I |
| F/M | 0.7464 | likely_pathogenic | 0.7481 | pathogenic | -0.848 | Destabilizing | 0.972 | D | 0.497 | neutral | None | None | None | None | I |
| F/N | 0.8349 | likely_pathogenic | 0.8374 | pathogenic | -2.4 | Highly Destabilizing | 0.92 | D | 0.549 | neutral | None | None | None | None | I |
| F/P | 0.9984 | likely_pathogenic | 0.999 | pathogenic | -1.367 | Destabilizing | 0.972 | D | 0.533 | neutral | None | None | None | None | I |
| F/Q | 0.8668 | likely_pathogenic | 0.8933 | pathogenic | -2.27 | Highly Destabilizing | 0.92 | D | 0.541 | neutral | None | None | None | None | I |
| F/R | 0.8392 | likely_pathogenic | 0.8797 | pathogenic | -1.541 | Destabilizing | 0.92 | D | 0.546 | neutral | None | None | None | None | I |
| F/S | 0.7307 | likely_pathogenic | 0.7232 | pathogenic | -3.079 | Highly Destabilizing | 0.549 | D | 0.548 | neutral | N | 0.480802987 | None | None | I |
| F/T | 0.7962 | likely_pathogenic | 0.7942 | pathogenic | -2.787 | Highly Destabilizing | 0.766 | D | 0.547 | neutral | None | None | None | None | I |
| F/V | 0.4203 | ambiguous | 0.4152 | ambiguous | -1.367 | Destabilizing | 0.549 | D | 0.496 | neutral | N | 0.477880186 | None | None | I |
| F/W | 0.6119 | likely_pathogenic | 0.5677 | pathogenic | -0.06 | Destabilizing | 0.92 | D | 0.499 | neutral | None | None | None | None | I |
| F/Y | 0.1075 | likely_benign | 0.09 | benign | -0.409 | Destabilizing | 0.001 | N | 0.121 | neutral | N | 0.372003515 | 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.