Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30969 | 93130;93131;93132 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| N2AB | 29328 | 88207;88208;88209 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| N2A | 28401 | 85426;85427;85428 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| N2B | 21904 | 65935;65936;65937 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| Novex-1 | 22029 | 66310;66311;66312 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| Novex-2 | 22096 | 66511;66512;66513 | chr2:178548721;178548720;178548719 | chr2:179413448;179413447;179413446 |
| 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/P | None | None | 0.992 | N | 0.422 | 0.341 | 0.349204839081 | gnomAD-4.0.0 | 6.84213E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99457E-07 | 0 | 0 |
| R/Q | rs751345368  |
0.114 | 0.924 | N | 0.361 | 0.229 | 0.184867976434 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs751345368 |
0.114 | 0.924 | N | 0.361 | 0.229 | 0.184867976434 | gnomAD-4.0.0 | 5.47371E-06 | None | None | None | None | N | None | 0 | 4.47247E-05 | None | 0 | 0 | None | 0 | 0 | 4.49728E-06 | 0 | 1.65656E-05 |
| R/W | rs754767262 |
-0.499 | 0.999 | N | 0.426 | 0.375 | 0.504848970537 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.77E-05 | 0 |
| R/W | rs754767262 |
-0.499 | 0.999 | N | 0.426 | 0.375 | 0.504848970537 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| R/W | rs754767262 |
-0.499 | 0.999 | N | 0.426 | 0.375 | 0.504848970537 | gnomAD-4.0.0 | 1.54913E-05 | None | None | None | None | N | None | 0 | 8.33028E-05 | None | 0 | 2.22866E-05 | None | 0 | 1.64962E-04 | 1.44092E-05 | 1.09794E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5829 | likely_pathogenic | 0.6481 | pathogenic | -0.569 | Destabilizing | 0.543 | D | 0.326 | neutral | None | None | None | None | N |
| R/C | 0.2326 | likely_benign | 0.2676 | benign | -0.532 | Destabilizing | 0.996 | D | 0.419 | neutral | None | None | None | None | N |
| R/D | 0.7655 | likely_pathogenic | 0.8087 | pathogenic | -0.029 | Destabilizing | 0.91 | D | 0.415 | neutral | None | None | None | None | N |
| R/E | 0.5358 | ambiguous | 0.5871 | pathogenic | 0.062 | Stabilizing | 0.742 | D | 0.301 | neutral | None | None | None | None | N |
| R/F | 0.6474 | likely_pathogenic | 0.7061 | pathogenic | -0.663 | Destabilizing | 0.91 | D | 0.441 | neutral | None | None | None | None | N |
| R/G | 0.4799 | ambiguous | 0.5384 | ambiguous | -0.832 | Destabilizing | 0.846 | D | 0.4 | neutral | N | 0.480880849 | None | None | N |
| R/H | 0.117 | likely_benign | 0.1412 | benign | -1.218 | Destabilizing | 0.009 | N | 0.22 | neutral | None | None | None | None | N |
| R/I | 0.4067 | ambiguous | 0.4488 | ambiguous | 0.113 | Stabilizing | 0.59 | D | 0.446 | neutral | None | None | None | None | N |
| R/K | 0.1672 | likely_benign | 0.1904 | benign | -0.542 | Destabilizing | 0.543 | D | 0.317 | neutral | None | None | None | None | N |
| R/L | 0.3159 | likely_benign | 0.3616 | ambiguous | 0.113 | Stabilizing | 0.532 | D | 0.313 | neutral | N | 0.489781619 | None | None | N |
| R/M | 0.4219 | ambiguous | 0.4593 | ambiguous | -0.136 | Destabilizing | 0.101 | N | 0.241 | neutral | None | None | None | None | N |
| R/N | 0.6793 | likely_pathogenic | 0.7399 | pathogenic | -0.033 | Destabilizing | 0.742 | D | 0.345 | neutral | None | None | None | None | N |
| R/P | 0.8229 | likely_pathogenic | 0.8554 | pathogenic | -0.093 | Destabilizing | 0.992 | D | 0.422 | neutral | N | 0.483958722 | None | None | N |
| R/Q | 0.1259 | likely_benign | 0.147 | benign | -0.257 | Destabilizing | 0.924 | D | 0.361 | neutral | N | 0.487819836 | None | None | N |
| R/S | 0.6628 | likely_pathogenic | 0.7237 | pathogenic | -0.723 | Destabilizing | 0.742 | D | 0.387 | neutral | None | None | None | None | N |
| R/T | 0.4 | ambiguous | 0.4651 | ambiguous | -0.468 | Destabilizing | 0.854 | D | 0.394 | neutral | None | None | None | None | N |
| R/V | 0.4951 | ambiguous | 0.5425 | ambiguous | -0.093 | Destabilizing | 0.59 | D | 0.419 | neutral | None | None | None | None | N |
| R/W | 0.2169 | likely_benign | 0.2432 | benign | -0.436 | Destabilizing | 0.999 | D | 0.426 | neutral | N | 0.497797016 | None | None | N |
| R/Y | 0.4391 | ambiguous | 0.5071 | ambiguous | -0.08 | Destabilizing | 0.835 | D | 0.412 | 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.