Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8817 | 26674;26675;26676 | chr2:178714325;178714324;178714323 | chr2:179579052;179579051;179579050 |
| N2AB | 8500 | 25723;25724;25725 | chr2:178714325;178714324;178714323 | chr2:179579052;179579051;179579050 |
| N2A | 7573 | 22942;22943;22944 | chr2:178714325;178714324;178714323 | chr2:179579052;179579051;179579050 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1427255919  |
-0.281 | None | N | 0.107 | 0.205 | 0.472181857204 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.9E-06 | 0 |
| M/I | rs1427255919 |
-0.281 | None | N | 0.107 | 0.205 | 0.472181857204 | gnomAD-4.0.0 | 3.18436E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86071E-06 | 1.43316E-05 | 0 |
| M/T | rs1469529188 |
-0.033 | None | N | 0.154 | 0.123 | 0.400468435593 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| M/T | rs1469529188 |
-0.033 | None | N | 0.154 | 0.123 | 0.400468435593 | gnomAD-4.0.0 | 9.58085E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25956E-05 | 0 | 0 |
| M/V | rs878856898 |
None | None | N | 0.105 | 0.081 | 0.395143324098 | gnomAD-4.0.0 | 1.5918E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85981E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2126 | likely_benign | 0.2322 | benign | -1.218 | Destabilizing | 0.016 | N | 0.21 | neutral | None | None | None | None | I |
| M/C | 0.6626 | likely_pathogenic | 0.681 | pathogenic | -0.87 | Destabilizing | 0.749 | D | 0.435 | neutral | None | None | None | None | I |
| M/D | 0.5587 | ambiguous | 0.5735 | pathogenic | -0.295 | Destabilizing | 0.148 | N | 0.514 | neutral | None | None | None | None | I |
| M/E | 0.2556 | likely_benign | 0.2682 | benign | -0.318 | Destabilizing | 0.148 | N | 0.445 | neutral | None | None | None | None | I |
| M/F | 0.1998 | likely_benign | 0.1959 | benign | -0.51 | Destabilizing | 0.001 | N | 0.114 | neutral | None | None | None | None | I |
| M/G | 0.3431 | ambiguous | 0.3669 | ambiguous | -1.457 | Destabilizing | 0.036 | N | 0.453 | neutral | None | None | None | None | I |
| M/H | 0.3068 | likely_benign | 0.3384 | benign | -0.502 | Destabilizing | 0.901 | D | 0.499 | neutral | None | None | None | None | I |
| M/I | 0.166 | likely_benign | 0.1555 | benign | -0.646 | Destabilizing | None | N | 0.107 | neutral | N | 0.466410478 | None | None | I |
| M/K | 0.1019 | likely_benign | 0.1253 | benign | -0.227 | Destabilizing | 0.116 | N | 0.385 | neutral | N | 0.437834223 | None | None | I |
| M/L | 0.0986 | likely_benign | 0.1053 | benign | -0.646 | Destabilizing | 0.005 | N | 0.141 | neutral | N | 0.484932315 | None | None | I |
| M/N | 0.255 | likely_benign | 0.2574 | benign | -0.032 | Destabilizing | 0.148 | N | 0.534 | neutral | None | None | None | None | I |
| M/P | 0.6869 | likely_pathogenic | 0.6994 | pathogenic | -0.809 | Destabilizing | 0.26 | N | 0.523 | neutral | None | None | None | None | I |
| M/Q | 0.1407 | likely_benign | 0.1524 | benign | -0.202 | Destabilizing | 0.296 | N | 0.378 | neutral | None | None | None | None | I |
| M/R | 0.1082 | likely_benign | 0.1301 | benign | 0.358 | Stabilizing | 0.241 | N | 0.489 | neutral | N | 0.500386978 | None | None | I |
| M/S | 0.1769 | likely_benign | 0.1868 | benign | -0.545 | Destabilizing | 0.001 | N | 0.161 | neutral | None | None | None | None | I |
| M/T | 0.104 | likely_benign | 0.1205 | benign | -0.469 | Destabilizing | None | N | 0.154 | neutral | N | 0.40899697 | None | None | I |
| M/V | 0.0768 | likely_benign | 0.0746 | benign | -0.809 | Destabilizing | None | N | 0.105 | neutral | N | 0.452865177 | None | None | I |
| M/W | 0.4584 | ambiguous | 0.4589 | ambiguous | -0.416 | Destabilizing | 0.901 | D | 0.455 | neutral | None | None | None | None | I |
| M/Y | 0.3924 | ambiguous | 0.3912 | ambiguous | -0.397 | Destabilizing | 0.08 | N | 0.483 | 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.