Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21299 | 64120;64121;64122 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| N2AB | 19658 | 59197;59198;59199 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| N2A | 18731 | 56416;56417;56418 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| N2B | 12234 | 36925;36926;36927 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| Novex-1 | 12359 | 37300;37301;37302 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| Novex-2 | 12426 | 37501;37502;37503 | chr2:178587316;178587315;178587314 | chr2:179452043;179452042;179452041 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs774568660  |
None | 0.989 | N | 0.455 | 0.351 | 0.44711355012 | gnomAD-4.0.0 | 1.59313E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86069E-06 | 0 | 0 |
| T/I | rs1031526299 |
0.048 | 0.956 | N | 0.616 | 0.377 | None | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 2.29674E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1031526299 |
0.048 | 0.956 | N | 0.616 | 0.377 | None | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1031526299 |
0.048 | 0.956 | N | 0.616 | 0.377 | None | gnomAD-4.0.0 | 5.13106E-06 | None | None | None | None | N | None | 6.77897E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1101 | likely_benign | 0.1198 | benign | -0.788 | Destabilizing | 0.989 | D | 0.455 | neutral | N | 0.482070435 | None | None | N |
| T/C | 0.4128 | ambiguous | 0.4259 | ambiguous | -0.413 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/D | 0.4867 | ambiguous | 0.5152 | ambiguous | -0.49 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | N |
| T/E | 0.391 | ambiguous | 0.4245 | ambiguous | -0.467 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/F | 0.3143 | likely_benign | 0.3217 | benign | -0.655 | Destabilizing | 0.995 | D | 0.773 | deleterious | None | None | None | None | N |
| T/G | 0.2395 | likely_benign | 0.2556 | benign | -1.083 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| T/H | 0.2625 | likely_benign | 0.2811 | benign | -1.346 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| T/I | 0.1702 | likely_benign | 0.1839 | benign | -0.08 | Destabilizing | 0.956 | D | 0.616 | neutral | N | 0.488700186 | None | None | N |
| T/K | 0.2071 | likely_benign | 0.2078 | benign | -0.948 | Destabilizing | 0.999 | D | 0.651 | neutral | D | 0.524100839 | None | None | N |
| T/L | 0.0924 | likely_benign | 0.0942 | benign | -0.08 | Destabilizing | 0.071 | N | 0.288 | neutral | None | None | None | None | N |
| T/M | 0.0951 | likely_benign | 0.0973 | benign | 0.155 | Stabilizing | 0.995 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/N | 0.1198 | likely_benign | 0.1344 | benign | -0.878 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| T/P | 0.4966 | ambiguous | 0.4538 | ambiguous | -0.283 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | N | 0.513305422 | None | None | N |
| T/Q | 0.241 | likely_benign | 0.2571 | benign | -0.965 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| T/R | 0.2308 | likely_benign | 0.2161 | benign | -0.74 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | N | 0.520580531 | None | None | N |
| T/S | 0.1036 | likely_benign | 0.1137 | benign | -1.097 | Destabilizing | 0.996 | D | 0.459 | neutral | N | 0.504360285 | None | None | N |
| T/V | 0.1492 | likely_benign | 0.158 | benign | -0.283 | Destabilizing | 0.967 | D | 0.43 | neutral | None | None | None | None | N |
| T/W | 0.7135 | likely_pathogenic | 0.7166 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| T/Y | 0.3694 | ambiguous | 0.3912 | ambiguous | -0.446 | Destabilizing | 0.999 | D | 0.771 | 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.