Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9966 | 30121;30122;30123 | chr2:178704576;178704575;178704574 | chr2:179569303;179569302;179569301 |
| N2AB | 9649 | 29170;29171;29172 | chr2:178704576;178704575;178704574 | chr2:179569303;179569302;179569301 |
| N2A | 8722 | 26389;26390;26391 | chr2:178704576;178704575;178704574 | chr2:179569303;179569302;179569301 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs1222395628  |
None | 0.001 | None | 0.107 | 0.102 | 0.0920862733494 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| K/I | rs1400936440 |
None | 0.007 | None | 0.169 | 0.16 | 0.295974979623 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| K/I | rs1400936440 |
None | 0.007 | None | 0.169 | 0.16 | 0.295974979623 | gnomAD-4.0.0 | 6.81735E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47683E-06 | 0 | 1.60113E-05 |
| K/R | rs1400936440 |
0.338 | 0.002 | None | 0.133 | 0.05 | 0.16115917748 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| K/R | rs1400936440 |
0.338 | 0.002 | None | 0.133 | 0.05 | 0.16115917748 | gnomAD-4.0.0 | 6.84319E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1605E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2321 | likely_benign | 0.2742 | benign | 0.037 | Stabilizing | 0.004 | N | 0.083 | neutral | None | None | None | None | N |
| K/C | 0.7894 | likely_pathogenic | 0.8484 | pathogenic | -0.065 | Destabilizing | 0.983 | D | 0.226 | neutral | None | None | None | None | N |
| K/D | 0.399 | ambiguous | 0.4334 | ambiguous | -0.046 | Destabilizing | 0.129 | N | 0.2 | neutral | None | None | None | None | N |
| K/E | 0.107 | likely_benign | 0.1153 | benign | -0.048 | Destabilizing | 0.001 | N | 0.107 | neutral | None | None | None | None | N |
| K/F | 0.7991 | likely_pathogenic | 0.8441 | pathogenic | -0.179 | Destabilizing | 0.716 | D | 0.318 | neutral | None | None | None | None | N |
| K/G | 0.3795 | ambiguous | 0.4338 | ambiguous | -0.159 | Destabilizing | 0.228 | N | 0.157 | neutral | None | None | None | None | N |
| K/H | 0.3409 | ambiguous | 0.3867 | ambiguous | -0.422 | Destabilizing | 0.716 | D | 0.245 | neutral | None | None | None | None | N |
| K/I | 0.3427 | ambiguous | 0.3963 | ambiguous | 0.474 | Stabilizing | 0.007 | N | 0.169 | neutral | None | None | None | None | N |
| K/L | 0.3437 | ambiguous | 0.4004 | ambiguous | 0.474 | Stabilizing | 0.129 | N | 0.167 | neutral | None | None | None | None | N |
| K/M | 0.2573 | likely_benign | 0.2835 | benign | 0.312 | Stabilizing | 0.836 | D | 0.247 | neutral | None | None | None | None | N |
| K/N | 0.2988 | likely_benign | 0.3301 | benign | 0.317 | Stabilizing | 0.351 | N | 0.194 | neutral | None | None | None | None | N |
| K/P | 0.4947 | ambiguous | 0.5897 | pathogenic | 0.356 | Stabilizing | 0.593 | D | 0.327 | neutral | None | None | None | None | N |
| K/Q | 0.1238 | likely_benign | 0.1371 | benign | 0.117 | Stabilizing | 0.003 | N | 0.104 | neutral | None | None | None | None | N |
| K/R | 0.0943 | likely_benign | 0.102 | benign | 0.031 | Stabilizing | 0.002 | N | 0.133 | neutral | None | None | None | None | N |
| K/S | 0.2789 | likely_benign | 0.3237 | benign | -0.141 | Destabilizing | 0.012 | N | 0.117 | neutral | None | None | None | None | N |
| K/T | 0.1612 | likely_benign | 0.1693 | benign | -0.001 | Destabilizing | 0.101 | N | 0.231 | neutral | None | None | None | None | N |
| K/V | 0.3305 | likely_benign | 0.3853 | ambiguous | 0.356 | Stabilizing | 0.129 | N | 0.154 | neutral | None | None | None | None | N |
| K/W | 0.7958 | likely_pathogenic | 0.8445 | pathogenic | -0.201 | Destabilizing | 0.983 | D | 0.229 | neutral | None | None | None | None | N |
| K/Y | 0.6982 | likely_pathogenic | 0.7517 | pathogenic | 0.149 | Stabilizing | 0.836 | D | 0.323 | neutral | 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.