Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24172 | 72739;72740;72741 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| N2AB | 22531 | 67816;67817;67818 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| N2A | 21604 | 65035;65036;65037 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| N2B | 15107 | 45544;45545;45546 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| Novex-1 | 15232 | 45919;45920;45921 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| Novex-2 | 15299 | 46120;46121;46122 | chr2:178573618;178573617;178573616 | chr2:179438345;179438344;179438343 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1457842450  |
0.066 | 0.684 | N | 0.375 | 0.176 | 0.267755039894 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| N/D | rs1457842450 |
0.066 | 0.684 | N | 0.375 | 0.176 | 0.267755039894 | gnomAD-4.0.0 | 3.99912E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.66084E-06 | 0 | 5.21231E-05 |
| N/S | rs772817909 |
-0.28 | 0.028 | N | 0.244 | 0.091 | 0.173771789658 | gnomAD-2.1.1 | 5.9E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.19E-05 | 0 |
| N/S | rs772817909 |
-0.28 | 0.028 | N | 0.244 | 0.091 | 0.173771789658 | gnomAD-4.0.0 | 1.94108E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.35983E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.132 | likely_benign | 0.1501 | benign | -0.587 | Destabilizing | 0.373 | N | 0.487 | neutral | None | None | None | None | N |
| N/C | 0.1848 | likely_benign | 0.241 | benign | 0.205 | Stabilizing | 0.996 | D | 0.595 | neutral | None | None | None | None | N |
| N/D | 0.1172 | likely_benign | 0.133 | benign | -0.21 | Destabilizing | 0.684 | D | 0.375 | neutral | N | 0.467167334 | None | None | N |
| N/E | 0.2966 | likely_benign | 0.3426 | ambiguous | -0.209 | Destabilizing | 0.742 | D | 0.353 | neutral | None | None | None | None | N |
| N/F | 0.4386 | ambiguous | 0.4947 | ambiguous | -0.706 | Destabilizing | 0.91 | D | 0.592 | neutral | None | None | None | None | N |
| N/G | 0.2268 | likely_benign | 0.2602 | benign | -0.825 | Destabilizing | 0.59 | D | 0.357 | neutral | None | None | None | None | N |
| N/H | 0.1126 | likely_benign | 0.1207 | benign | -0.747 | Destabilizing | 0.015 | N | 0.263 | neutral | N | 0.477805615 | None | None | N |
| N/I | 0.1308 | likely_benign | 0.1475 | benign | -0.03 | Destabilizing | 0.521 | D | 0.548 | neutral | N | 0.424493992 | None | None | N |
| N/K | 0.3244 | likely_benign | 0.3905 | ambiguous | -0.101 | Destabilizing | 0.684 | D | 0.409 | neutral | N | 0.439076656 | None | None | N |
| N/L | 0.1664 | likely_benign | 0.187 | benign | -0.03 | Destabilizing | 0.59 | D | 0.509 | neutral | None | None | None | None | N |
| N/M | 0.2058 | likely_benign | 0.2379 | benign | 0.443 | Stabilizing | 0.987 | D | 0.588 | neutral | None | None | None | None | N |
| N/P | 0.409 | ambiguous | 0.47 | ambiguous | -0.188 | Destabilizing | 0.953 | D | 0.593 | neutral | None | None | None | None | N |
| N/Q | 0.2878 | likely_benign | 0.331 | benign | -0.678 | Destabilizing | 0.953 | D | 0.455 | neutral | None | None | None | None | N |
| N/R | 0.3577 | ambiguous | 0.4334 | ambiguous | -0.005 | Destabilizing | 0.91 | D | 0.439 | neutral | None | None | None | None | N |
| N/S | 0.0695 | likely_benign | 0.0749 | benign | -0.468 | Destabilizing | 0.028 | N | 0.244 | neutral | N | 0.464703032 | None | None | N |
| N/T | 0.0848 | likely_benign | 0.096 | benign | -0.308 | Destabilizing | 0.521 | D | 0.353 | neutral | N | 0.391706783 | None | None | N |
| N/V | 0.1146 | likely_benign | 0.1225 | benign | -0.188 | Destabilizing | 0.009 | N | 0.388 | neutral | None | None | None | None | N |
| N/W | 0.6893 | likely_pathogenic | 0.7585 | pathogenic | -0.556 | Destabilizing | 0.996 | D | 0.672 | neutral | None | None | None | None | N |
| N/Y | 0.1474 | likely_benign | 0.1694 | benign | -0.344 | Destabilizing | 0.884 | D | 0.6 | neutral | N | 0.494988654 | 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.