Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5527 | 16804;16805;16806 | chr2:178732482;178732481;178732480 | chr2:179597209;179597208;179597207 |
| N2AB | 5210 | 15853;15854;15855 | chr2:178732482;178732481;178732480 | chr2:179597209;179597208;179597207 |
| N2A | 4283 | 13072;13073;13074 | chr2:178732482;178732481;178732480 | chr2:179597209;179597208;179597207 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs541467635  |
-0.118 | None | N | 0.147 | 0.133 | 0.446310458034 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs541467635 |
-0.118 | None | N | 0.147 | 0.133 | 0.446310458034 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs541467635 |
-0.118 | None | N | 0.147 | 0.133 | 0.446310458034 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/A | rs541467635 |
-0.118 | None | N | 0.147 | 0.133 | 0.446310458034 | gnomAD-4.0.0 | 6.56564E-06 | None | None | None | None | I | None | 2.40512E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1334663895 |
-0.139 | None | N | 0.251 | 0.086 | 0.306377322295 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs1334663895 |
-0.139 | None | N | 0.251 | 0.086 | 0.306377322295 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs1334663895 |
-0.139 | None | N | 0.251 | 0.086 | 0.306377322295 | gnomAD-4.0.0 | 5.12909E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.4266E-05 | None | 0 | 0 | 7.18725E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0765 | likely_benign | 0.0881 | benign | -0.363 | Destabilizing | None | N | 0.147 | neutral | N | 0.386813544 | None | None | I |
| V/C | 0.6501 | likely_pathogenic | 0.6931 | pathogenic | -0.847 | Destabilizing | 0.824 | D | 0.343 | neutral | None | None | None | None | I |
| V/D | 0.1425 | likely_benign | 0.1686 | benign | -0.332 | Destabilizing | None | N | 0.185 | neutral | N | 0.37727134 | None | None | I |
| V/E | 0.1464 | likely_benign | 0.1743 | benign | -0.449 | Destabilizing | 0.081 | N | 0.389 | neutral | None | None | None | None | I |
| V/F | 0.1212 | likely_benign | 0.1346 | benign | -0.774 | Destabilizing | 0.317 | N | 0.345 | neutral | N | 0.477435548 | None | None | I |
| V/G | 0.1235 | likely_benign | 0.1361 | benign | -0.4 | Destabilizing | 0.062 | N | 0.388 | neutral | N | 0.430604393 | None | None | I |
| V/H | 0.3188 | likely_benign | 0.3554 | ambiguous | -0.047 | Destabilizing | 0.935 | D | 0.319 | neutral | None | None | None | None | I |
| V/I | 0.0715 | likely_benign | 0.077 | benign | -0.402 | Destabilizing | None | N | 0.251 | neutral | N | 0.438666516 | None | None | I |
| V/K | 0.1583 | likely_benign | 0.1827 | benign | -0.365 | Destabilizing | 0.149 | N | 0.349 | neutral | None | None | None | None | I |
| V/L | 0.135 | likely_benign | 0.152 | benign | -0.402 | Destabilizing | 0.009 | N | 0.337 | neutral | N | 0.452057101 | None | None | I |
| V/M | 0.106 | likely_benign | 0.1201 | benign | -0.585 | Destabilizing | 0.38 | N | 0.303 | neutral | None | None | None | None | I |
| V/N | 0.131 | likely_benign | 0.1552 | benign | -0.186 | Destabilizing | 0.38 | N | 0.35 | neutral | None | None | None | None | I |
| V/P | 0.2659 | likely_benign | 0.2939 | benign | -0.364 | Destabilizing | 0.38 | N | 0.372 | neutral | None | None | None | None | I |
| V/Q | 0.1836 | likely_benign | 0.1971 | benign | -0.391 | Destabilizing | 0.555 | D | 0.371 | neutral | None | None | None | None | I |
| V/R | 0.1428 | likely_benign | 0.1526 | benign | 0.055 | Stabilizing | 0.38 | N | 0.35 | neutral | None | None | None | None | I |
| V/S | 0.105 | likely_benign | 0.1215 | benign | -0.498 | Destabilizing | 0.081 | N | 0.373 | neutral | None | None | None | None | I |
| V/T | 0.1005 | likely_benign | 0.1165 | benign | -0.527 | Destabilizing | 0.002 | N | 0.22 | neutral | None | None | None | None | I |
| V/W | 0.6076 | likely_pathogenic | 0.6549 | pathogenic | -0.814 | Destabilizing | 0.935 | D | 0.406 | neutral | None | None | None | None | I |
| V/Y | 0.3655 | ambiguous | 0.4045 | ambiguous | -0.554 | Destabilizing | 0.555 | D | 0.343 | 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.