Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1348 | 4267;4268;4269 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| N2AB | 1348 | 4267;4268;4269 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| N2A | 1348 | 4267;4268;4269 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| N2B | 1302 | 4129;4130;4131 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| Novex-1 | 1302 | 4129;4130;4131 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| Novex-2 | 1302 | 4129;4130;4131 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
| Novex-3 | 1348 | 4267;4268;4269 | chr2:178779040;178779039;178779038 | chr2:179643767;179643766;179643765 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs397517591  |
-1.127 | 0.822 | N | 0.547 | 0.396 | 0.351180957027 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 3.27439E-04 |
| S/G | rs397517591 |
-1.127 | 0.822 | N | 0.547 | 0.396 | 0.351180957027 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| S/G | rs397517591 |
-1.127 | 0.822 | N | 0.547 | 0.396 | 0.351180957027 | gnomAD-4.0.0 | 1.5368E-05 | None | None | None | None | N | None | 0 | 5.08423E-05 | None | 0 | 0 | None | 0 | 0 | 1.67437E-05 | 1.34005E-05 | 2.84188E-05 |
| S/T | None | None | 0.014 | N | 0.405 | 0.096 | 0.184867976434 | gnomAD-4.0.0 | 1.59085E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1575 | likely_benign | 0.1959 | benign | -0.671 | Destabilizing | 0.559 | D | 0.489 | neutral | None | None | None | None | N |
| S/C | 0.2488 | likely_benign | 0.3026 | benign | -0.468 | Destabilizing | 0.997 | D | 0.696 | prob.neutral | D | 0.545178927 | None | None | N |
| S/D | 0.9166 | likely_pathogenic | 0.9531 | pathogenic | -1.132 | Destabilizing | 0.86 | D | 0.552 | neutral | None | None | None | None | N |
| S/E | 0.8968 | likely_pathogenic | 0.9397 | pathogenic | -1.005 | Destabilizing | 0.86 | D | 0.571 | neutral | None | None | None | None | N |
| S/F | 0.4904 | ambiguous | 0.6261 | pathogenic | -0.598 | Destabilizing | 0.978 | D | 0.747 | deleterious | None | None | None | None | N |
| S/G | 0.3666 | ambiguous | 0.4587 | ambiguous | -1.047 | Destabilizing | 0.822 | D | 0.547 | neutral | N | 0.507899912 | None | None | N |
| S/H | 0.7173 | likely_pathogenic | 0.8067 | pathogenic | -1.588 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/I | 0.4046 | ambiguous | 0.5218 | ambiguous | 0.257 | Stabilizing | 0.89 | D | 0.704 | prob.neutral | N | 0.517423282 | None | None | N |
| S/K | 0.9674 | likely_pathogenic | 0.9823 | pathogenic | -0.534 | Destabilizing | 0.86 | D | 0.557 | neutral | None | None | None | None | N |
| S/L | 0.2899 | likely_benign | 0.3831 | ambiguous | 0.257 | Stabilizing | 0.754 | D | 0.643 | neutral | None | None | None | None | N |
| S/M | 0.3961 | ambiguous | 0.4949 | ambiguous | 0.394 | Stabilizing | 0.994 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/N | 0.5831 | likely_pathogenic | 0.7027 | pathogenic | -1.001 | Destabilizing | 0.822 | D | 0.55 | neutral | N | 0.511396699 | None | None | N |
| S/P | 0.9952 | likely_pathogenic | 0.9965 | pathogenic | -0.015 | Destabilizing | 0.978 | D | 0.645 | neutral | None | None | None | None | N |
| S/Q | 0.8455 | likely_pathogenic | 0.8992 | pathogenic | -0.867 | Destabilizing | 0.978 | D | 0.635 | neutral | None | None | None | None | N |
| S/R | 0.9366 | likely_pathogenic | 0.9639 | pathogenic | -0.786 | Destabilizing | 0.942 | D | 0.653 | neutral | N | 0.514371176 | None | None | N |
| S/T | 0.1356 | likely_benign | 0.1772 | benign | -0.725 | Destabilizing | 0.014 | N | 0.405 | neutral | N | 0.488989915 | None | None | N |
| S/V | 0.3373 | likely_benign | 0.4429 | ambiguous | -0.015 | Destabilizing | 0.915 | D | 0.671 | neutral | None | None | None | None | N |
| S/W | 0.7352 | likely_pathogenic | 0.8128 | pathogenic | -0.807 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| S/Y | 0.5085 | ambiguous | 0.6245 | pathogenic | -0.411 | Destabilizing | 0.978 | D | 0.751 | 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.