Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18470 | 55633;55634;55635 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| N2AB | 16829 | 50710;50711;50712 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| N2A | 15902 | 47929;47930;47931 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| N2B | 9405 | 28438;28439;28440 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| Novex-1 | 9530 | 28813;28814;28815 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| Novex-2 | 9597 | 29014;29015;29016 | chr2:178601682;178601681;178601680 | chr2:179466409;179466408;179466407 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs1447736099  |
None | 0.801 | N | 0.521 | 0.264 | 0.294206760003 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs1374641956 |
0.055 | 0.002 | N | 0.221 | 0.114 | None | gnomAD-2.1.1 | 4.21E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.84E-05 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs1374641956 |
0.055 | 0.002 | N | 0.221 | 0.114 | None | gnomAD-4.0.0 | 1.17247E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.29988E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5049 | ambiguous | 0.4799 | ambiguous | -0.8 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | I |
| A/D | 0.7416 | likely_pathogenic | 0.7769 | pathogenic | -0.284 | Destabilizing | 0.991 | D | 0.736 | prob.delet. | None | None | None | None | I |
| A/E | 0.5673 | likely_pathogenic | 0.6042 | pathogenic | -0.422 | Destabilizing | 0.891 | D | 0.633 | neutral | D | 0.535195772 | None | None | I |
| A/F | 0.5062 | ambiguous | 0.4957 | ambiguous | -0.982 | Destabilizing | 0.949 | D | 0.749 | deleterious | None | None | None | None | I |
| A/G | 0.2328 | likely_benign | 0.2352 | benign | -0.48 | Destabilizing | 0.891 | D | 0.529 | neutral | N | 0.489939653 | None | None | I |
| A/H | 0.7446 | likely_pathogenic | 0.75 | pathogenic | -0.51 | Destabilizing | 0.998 | D | 0.728 | prob.delet. | None | None | None | None | I |
| A/I | 0.2758 | likely_benign | 0.2537 | benign | -0.393 | Destabilizing | 0.525 | D | 0.542 | neutral | None | None | None | None | I |
| A/K | 0.7124 | likely_pathogenic | 0.7173 | pathogenic | -0.566 | Destabilizing | 0.915 | D | 0.631 | neutral | None | None | None | None | I |
| A/L | 0.2885 | likely_benign | 0.2743 | benign | -0.393 | Destabilizing | 0.525 | D | 0.511 | neutral | None | None | None | None | I |
| A/M | 0.3121 | likely_benign | 0.294 | benign | -0.394 | Destabilizing | 0.974 | D | 0.671 | neutral | None | None | None | None | I |
| A/N | 0.6134 | likely_pathogenic | 0.6156 | pathogenic | -0.273 | Destabilizing | 0.991 | D | 0.747 | deleterious | None | None | None | None | I |
| A/P | 0.9817 | likely_pathogenic | 0.9865 | pathogenic | -0.362 | Destabilizing | 0.989 | D | 0.663 | neutral | N | 0.508132813 | None | None | I |
| A/Q | 0.5384 | ambiguous | 0.5505 | ambiguous | -0.529 | Destabilizing | 0.991 | D | 0.669 | neutral | None | None | None | None | I |
| A/R | 0.6307 | likely_pathogenic | 0.6536 | pathogenic | -0.147 | Destabilizing | 0.974 | D | 0.675 | neutral | None | None | None | None | I |
| A/S | 0.1417 | likely_benign | 0.1356 | benign | -0.539 | Destabilizing | 0.891 | D | 0.56 | neutral | N | 0.502717994 | None | None | I |
| A/T | 0.1065 | likely_benign | 0.106 | benign | -0.587 | Destabilizing | 0.801 | D | 0.521 | neutral | N | 0.519938318 | None | None | I |
| A/V | 0.1278 | likely_benign | 0.1211 | benign | -0.362 | Destabilizing | 0.002 | N | 0.221 | neutral | N | 0.443960479 | None | None | I |
| A/W | 0.88 | likely_pathogenic | 0.8832 | pathogenic | -1.115 | Destabilizing | 0.998 | D | 0.78 | deleterious | None | None | None | None | I |
| A/Y | 0.7048 | likely_pathogenic | 0.7066 | pathogenic | -0.755 | Destabilizing | 0.974 | D | 0.749 | deleterious | None | None | None | None | I |
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.