Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31653 | 95182;95183;95184 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| N2AB | 30012 | 90259;90260;90261 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| N2A | 29085 | 87478;87479;87480 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| N2B | 22588 | 67987;67988;67989 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| Novex-1 | 22713 | 68362;68363;68364 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| Novex-2 | 22780 | 68563;68564;68565 | chr2:178546374;178546373;178546372 | chr2:179411101;179411100;179411099 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs546302731  |
-0.176 | 0.067 | N | 0.303 | 0.094 | 0.195762928549 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3071E-04 | None | 0 | 0 | 0 |
| D/E | rs546302731 |
-0.176 | 0.067 | N | 0.303 | 0.094 | 0.195762928549 | gnomAD-4.0.0 | 4.78951E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11557E-05 | 0 |
| D/N | rs1697134588 |
None | 0.988 | N | 0.662 | 0.263 | 0.195762928549 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs1697134588 |
None | 0.988 | N | 0.662 | 0.263 | 0.195762928549 | gnomAD-4.0.0 | 2.5623E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.42401E-05 | None | 0 | 0 | 2.39313E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.133 | likely_benign | 0.1426 | benign | 0.086 | Stabilizing | 0.958 | D | 0.607 | neutral | N | 0.458934571 | None | None | N |
| D/C | 0.4824 | ambiguous | 0.4998 | ambiguous | -0.072 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/E | 0.0968 | likely_benign | 0.1036 | benign | -0.37 | Destabilizing | 0.067 | N | 0.303 | neutral | N | 0.458632704 | None | None | N |
| D/F | 0.4884 | ambiguous | 0.5112 | ambiguous | -0.112 | Destabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| D/G | 0.1006 | likely_benign | 0.1008 | benign | 0.014 | Stabilizing | 0.958 | D | 0.652 | neutral | N | 0.397594527 | None | None | N |
| D/H | 0.2405 | likely_benign | 0.2511 | benign | 0.466 | Stabilizing | 0.998 | D | 0.644 | neutral | N | 0.484293755 | None | None | N |
| D/I | 0.2479 | likely_benign | 0.2782 | benign | 0.202 | Stabilizing | 0.995 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/K | 0.2415 | likely_benign | 0.2543 | benign | 0.435 | Stabilizing | 0.982 | D | 0.675 | neutral | None | None | None | None | N |
| D/L | 0.2632 | likely_benign | 0.2894 | benign | 0.202 | Stabilizing | 0.991 | D | 0.67 | neutral | None | None | None | None | N |
| D/M | 0.3985 | ambiguous | 0.4403 | ambiguous | 0.047 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/N | 0.0789 | likely_benign | 0.081 | benign | 0.304 | Stabilizing | 0.988 | D | 0.662 | neutral | N | 0.467174829 | None | None | N |
| D/P | 0.4495 | ambiguous | 0.4759 | ambiguous | 0.18 | Stabilizing | 0.995 | D | 0.668 | neutral | None | None | None | None | N |
| D/Q | 0.196 | likely_benign | 0.2135 | benign | 0.283 | Stabilizing | 0.982 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/R | 0.2855 | likely_benign | 0.2942 | benign | 0.568 | Stabilizing | 0.991 | D | 0.623 | neutral | None | None | None | None | N |
| D/S | 0.0954 | likely_benign | 0.0995 | benign | 0.205 | Stabilizing | 0.968 | D | 0.596 | neutral | None | None | None | None | N |
| D/T | 0.1607 | likely_benign | 0.1776 | benign | 0.269 | Stabilizing | 0.991 | D | 0.678 | prob.neutral | None | None | None | None | N |
| D/V | 0.1611 | likely_benign | 0.1774 | benign | 0.18 | Stabilizing | 0.994 | D | 0.674 | neutral | N | 0.484800734 | None | None | N |
| D/W | 0.7788 | likely_pathogenic | 0.7917 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2264 | likely_benign | 0.2267 | benign | 0.095 | Stabilizing | 0.999 | D | 0.664 | neutral | N | 0.477799295 | 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.