Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18510 | 55753;55754;55755 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| N2AB | 16869 | 50830;50831;50832 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| N2A | 15942 | 48049;48050;48051 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| N2B | 9445 | 28558;28559;28560 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| Novex-1 | 9570 | 28933;28934;28935 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| Novex-2 | 9637 | 29134;29135;29136 | chr2:178601469;178601468;178601467 | chr2:179466196;179466195;179466194 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/S | rs1165541106  |
0.085 | 0.989 | N | 0.593 | 0.311 | 0.248417906384 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/S | rs1165541106 |
0.085 | 0.989 | N | 0.593 | 0.311 | 0.248417906384 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/S | rs1165541106 |
0.085 | 0.989 | N | 0.593 | 0.311 | 0.248417906384 | gnomAD-4.0.0 | 5.58006E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63134E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7013 | likely_pathogenic | 0.6853 | pathogenic | 0.1 | Stabilizing | 0.992 | D | 0.622 | neutral | None | None | None | None | I |
| R/C | 0.4063 | ambiguous | 0.3817 | ambiguous | 0.024 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| R/D | 0.8695 | likely_pathogenic | 0.8726 | pathogenic | -0.063 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| R/E | 0.6904 | likely_pathogenic | 0.6898 | pathogenic | 0.016 | Stabilizing | 0.992 | D | 0.59 | neutral | None | None | None | None | I |
| R/F | 0.7925 | likely_pathogenic | 0.8148 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/G | 0.6164 | likely_pathogenic | 0.6212 | pathogenic | -0.12 | Destabilizing | 0.994 | D | 0.557 | neutral | N | 0.468167412 | None | None | I |
| R/H | 0.2087 | likely_benign | 0.1958 | benign | -0.715 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
| R/I | 0.5329 | ambiguous | 0.5247 | ambiguous | 0.649 | Stabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| R/K | 0.1785 | likely_benign | 0.1676 | benign | 0.05 | Stabilizing | 0.543 | D | 0.285 | neutral | N | 0.450888373 | None | None | I |
| R/L | 0.5186 | ambiguous | 0.5193 | ambiguous | 0.649 | Stabilizing | 0.996 | D | 0.557 | neutral | None | None | None | None | I |
| R/M | 0.5668 | likely_pathogenic | 0.5587 | ambiguous | 0.136 | Stabilizing | 1.0 | D | 0.603 | neutral | N | 0.489428118 | None | None | I |
| R/N | 0.8127 | likely_pathogenic | 0.8099 | pathogenic | 0.295 | Stabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | I |
| R/P | 0.679 | likely_pathogenic | 0.6556 | pathogenic | 0.488 | Stabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| R/Q | 0.2341 | likely_benign | 0.2234 | benign | 0.229 | Stabilizing | 0.998 | D | 0.59 | neutral | None | None | None | None | I |
| R/S | 0.8077 | likely_pathogenic | 0.7979 | pathogenic | -0.007 | Destabilizing | 0.989 | D | 0.593 | neutral | N | 0.471610362 | None | None | I |
| R/T | 0.5974 | likely_pathogenic | 0.5656 | pathogenic | 0.213 | Stabilizing | 0.998 | D | 0.57 | neutral | N | 0.475824103 | None | None | I |
| R/V | 0.6173 | likely_pathogenic | 0.5933 | pathogenic | 0.488 | Stabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/W | 0.3907 | ambiguous | 0.4314 | ambiguous | -0.093 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.485447342 | None | None | I |
| R/Y | 0.6253 | likely_pathogenic | 0.6551 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.667 | neutral | 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.