Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14314 | 43165;43166;43167 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| N2AB | 12673 | 38242;38243;38244 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| N2A | 11746 | 35461;35462;35463 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| N2B | 5249 | 15970;15971;15972 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| Novex-1 | 5374 | 16345;16346;16347 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| Novex-2 | 5441 | 16546;16547;16548 | chr2:178633419;178633418;178633417 | chr2:179498146;179498145;179498144 |
| 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 | rs1317914021  |
-1.999 | 0.517 | D | 0.602 | 0.436 | 0.650830185303 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1317914021 |
-1.999 | 0.517 | D | 0.602 | 0.436 | 0.650830185303 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs1317914021 |
-1.999 | 0.517 | D | 0.602 | 0.436 | 0.650830185303 | gnomAD-4.0.0 | 1.85958E-06 | None | None | None | None | N | None | 2.67051E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47777E-07 | 0 | 0 |
| V/I | rs376881525 |
-0.769 | 0.003 | N | 0.315 | 0.119 | None | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.33E-05 | 0 |
| V/I | rs376881525 |
-0.769 | 0.003 | N | 0.315 | 0.119 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs376881525 |
-0.769 | 0.003 | N | 0.315 | 0.119 | None | gnomAD-4.0.0 | 3.96707E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.34092E-05 | 0 | 1.602E-05 |
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 | 0.5795 | likely_pathogenic | 0.5298 | ambiguous | -1.843 | Destabilizing | 0.517 | D | 0.602 | neutral | D | 0.681261278 | None | None | N |
| V/C | 0.942 | likely_pathogenic | 0.9244 | pathogenic | -1.705 | Destabilizing | 0.996 | D | 0.634 | neutral | None | None | None | None | N |
| V/D | 0.984 | likely_pathogenic | 0.9854 | pathogenic | -2.841 | Highly Destabilizing | 0.983 | D | 0.707 | prob.neutral | D | 0.74277586 | None | None | N |
| V/E | 0.9579 | likely_pathogenic | 0.9579 | pathogenic | -2.783 | Highly Destabilizing | 0.987 | D | 0.65 | neutral | None | None | None | None | N |
| V/F | 0.6275 | likely_pathogenic | 0.597 | pathogenic | -1.295 | Destabilizing | 0.901 | D | 0.641 | neutral | D | 0.742082187 | None | None | N |
| V/G | 0.8111 | likely_pathogenic | 0.7994 | pathogenic | -2.19 | Highly Destabilizing | 0.949 | D | 0.677 | prob.neutral | D | 0.74277586 | None | None | N |
| V/H | 0.9871 | likely_pathogenic | 0.987 | pathogenic | -1.623 | Destabilizing | 0.996 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/I | 0.0868 | likely_benign | 0.0824 | benign | -0.939 | Destabilizing | 0.003 | N | 0.315 | neutral | N | 0.471756241 | None | None | N |
| V/K | 0.9657 | likely_pathogenic | 0.9697 | pathogenic | -1.526 | Destabilizing | 0.961 | D | 0.653 | neutral | None | None | None | None | N |
| V/L | 0.4485 | ambiguous | 0.3839 | ambiguous | -0.939 | Destabilizing | 0.075 | N | 0.425 | neutral | D | 0.595762693 | None | None | N |
| V/M | 0.3774 | ambiguous | 0.3213 | benign | -1.014 | Destabilizing | 0.923 | D | 0.664 | neutral | None | None | None | None | N |
| V/N | 0.9485 | likely_pathogenic | 0.9461 | pathogenic | -1.629 | Destabilizing | 0.987 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/P | 0.9608 | likely_pathogenic | 0.9575 | pathogenic | -1.212 | Destabilizing | 0.987 | D | 0.645 | neutral | None | None | None | None | N |
| V/Q | 0.9586 | likely_pathogenic | 0.9582 | pathogenic | -1.786 | Destabilizing | 0.987 | D | 0.663 | neutral | None | None | None | None | N |
| V/R | 0.9434 | likely_pathogenic | 0.9514 | pathogenic | -1.048 | Destabilizing | 0.987 | D | 0.712 | prob.delet. | None | None | None | None | N |
| V/S | 0.8303 | likely_pathogenic | 0.8116 | pathogenic | -2.06 | Highly Destabilizing | 0.961 | D | 0.629 | neutral | None | None | None | None | N |
| V/T | 0.5925 | likely_pathogenic | 0.5584 | ambiguous | -1.902 | Destabilizing | 0.775 | D | 0.621 | neutral | None | None | None | None | N |
| V/W | 0.9876 | likely_pathogenic | 0.9859 | pathogenic | -1.574 | Destabilizing | 0.996 | D | 0.686 | prob.neutral | None | None | None | None | N |
| V/Y | 0.9583 | likely_pathogenic | 0.9547 | pathogenic | -1.286 | Destabilizing | 0.961 | D | 0.649 | 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.