Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35909 | 107950;107951;107952 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| N2AB | 34268 | 103027;103028;103029 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| N2A | 33341 | 100246;100247;100248 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| N2B | 26844 | 80755;80756;80757 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| Novex-1 | 26969 | 81130;81131;81132 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| Novex-2 | 27036 | 81331;81332;81333 | chr2:178527263;178527262;178527261 | chr2:179391990;179391989;179391988 |
| 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 | rs1401685434  |
None | 0.001 | N | 0.24 | 0.111 | 0.0611884634855 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | -0.25(OBSL1) -0.412(OBSCN) | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs1401685434 |
None | 0.001 | N | 0.24 | 0.111 | 0.0611884634855 | gnomAD-4.0.0 | 3.04467E-06 | None | None | None | -0.25(OBSL1) -0.412(OBSCN) | N | None | 5.24054E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2942 | likely_benign | 0.3464 | ambiguous | -0.5 | Destabilizing | 0.001 | N | 0.335 | neutral | N | 0.454673331 | None | -0.671(OBSL1) -0.379(OBSCN) | N |
| D/C | 0.8659 | likely_pathogenic | 0.8906 | pathogenic | -0.14 | Destabilizing | 0.944 | D | 0.467 | neutral | None | None | None | -0.907(OBSL1) -0.485(OBSCN) | N |
| D/E | 0.2657 | likely_benign | 0.3163 | benign | -0.398 | Destabilizing | 0.001 | N | 0.24 | neutral | N | 0.39416359 | None | -0.25(OBSL1) -0.412(OBSCN) | N |
| D/F | 0.8354 | likely_pathogenic | 0.8544 | pathogenic | -0.113 | Destabilizing | 0.818 | D | 0.455 | neutral | None | None | None | -1.032(OBSL1) -0.988(OBSCN) | N |
| D/G | 0.3288 | likely_benign | 0.3798 | ambiguous | -0.782 | Destabilizing | 0.193 | N | 0.352 | neutral | N | 0.509585252 | None | -0.772(OBSL1) -0.492(OBSCN) | N |
| D/H | 0.4875 | ambiguous | 0.5242 | ambiguous | -0.115 | Destabilizing | 0.773 | D | 0.413 | neutral | N | 0.480302495 | None | 0.0(OBSL1) 0.32(OBSCN) | N |
| D/I | 0.6754 | likely_pathogenic | 0.7237 | pathogenic | 0.224 | Stabilizing | 0.69 | D | 0.453 | neutral | None | None | None | -0.423(OBSL1) -0.075(OBSCN) | N |
| D/K | 0.6105 | likely_pathogenic | 0.6694 | pathogenic | 0.114 | Stabilizing | 0.241 | N | 0.349 | neutral | None | None | None | -0.628(OBSL1) -0.268(OBSCN) | N |
| D/L | 0.619 | likely_pathogenic | 0.6602 | pathogenic | 0.224 | Stabilizing | 0.241 | N | 0.415 | neutral | None | None | None | -0.423(OBSL1) -0.075(OBSCN) | N |
| D/M | 0.8455 | likely_pathogenic | 0.878 | pathogenic | 0.447 | Stabilizing | 0.981 | D | 0.453 | neutral | None | None | None | 0.402(OBSL1) 1.164(OBSCN) | N |
| D/N | 0.1714 | likely_benign | 0.202 | benign | -0.414 | Destabilizing | 0.324 | N | 0.357 | neutral | N | 0.446035205 | None | -0.661(OBSL1) -1.434(OBSCN) | N |
| D/P | 0.7651 | likely_pathogenic | 0.8086 | pathogenic | 0.006 | Stabilizing | 0.818 | D | 0.385 | neutral | None | None | None | -0.495(OBSL1) -0.168(OBSCN) | N |
| D/Q | 0.5446 | ambiguous | 0.6062 | pathogenic | -0.322 | Destabilizing | 0.054 | N | 0.287 | neutral | None | None | None | -0.528(OBSL1) -1.008(OBSCN) | N |
| D/R | 0.6066 | likely_pathogenic | 0.6655 | pathogenic | 0.331 | Stabilizing | 0.69 | D | 0.435 | neutral | None | None | None | -0.404(OBSL1) -0.039(OBSCN) | N |
| D/S | 0.1929 | likely_benign | 0.2296 | benign | -0.557 | Destabilizing | 0.116 | N | 0.301 | neutral | None | None | None | -1.134(OBSL1) -1.409(OBSCN) | N |
| D/T | 0.4407 | ambiguous | 0.5053 | ambiguous | -0.322 | Destabilizing | 0.388 | N | 0.353 | neutral | None | None | None | -1.054(OBSL1) -1.291(OBSCN) | N |
| D/V | 0.4512 | ambiguous | 0.5009 | ambiguous | 0.006 | Stabilizing | 0.193 | N | 0.417 | neutral | N | 0.439186591 | None | -0.495(OBSL1) -0.168(OBSCN) | N |
| D/W | 0.9552 | likely_pathogenic | 0.9607 | pathogenic | 0.131 | Stabilizing | 0.981 | D | 0.521 | neutral | None | None | None | -1.32(OBSL1) -1.365(OBSCN) | N |
| D/Y | 0.4493 | ambiguous | 0.4513 | ambiguous | 0.155 | Stabilizing | 0.912 | D | 0.454 | neutral | N | 0.488999336 | None | -0.91(OBSL1) -1.0(OBSCN) | 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.