Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15806 | 47641;47642;47643 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| N2AB | 14165 | 42718;42719;42720 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| N2A | 13238 | 39937;39938;39939 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| N2B | 6741 | 20446;20447;20448 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| Novex-1 | 6866 | 20821;20822;20823 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| Novex-2 | 6933 | 21022;21023;21024 | chr2:178617935;178617934;178617933 | chr2:179482662;179482661;179482660 |
| 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/N | rs773892971  |
-0.255 | 0.117 | N | 0.28 | 0.148 | 0.244539031024 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| D/N | rs773892971 |
-0.255 | 0.117 | N | 0.28 | 0.148 | 0.244539031024 | gnomAD-4.0.0 | 6.84583E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99897E-07 | 0 | 0 |
| D/Y | rs773892971 |
0.087 | 0.741 | N | 0.381 | 0.234 | 0.432826170204 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| D/Y | rs773892971 |
0.087 | 0.741 | N | 0.381 | 0.234 | 0.432826170204 | gnomAD-4.0.0 | 4.1075E-06 | None | None | None | None | N | None | 0 | 2.23754E-05 | None | 0 | 2.52334E-05 | None | 0 | 0 | 8.99897E-07 | 3.47891E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1611 | likely_benign | 0.1645 | benign | -0.635 | Destabilizing | 0.002 | N | 0.215 | neutral | N | 0.45961545 | None | None | N |
| D/C | 0.6571 | likely_pathogenic | 0.6192 | pathogenic | -0.261 | Destabilizing | 0.935 | D | 0.369 | neutral | None | None | None | None | N |
| D/E | 0.0987 | likely_benign | 0.0925 | benign | -0.541 | Destabilizing | None | N | 0.099 | neutral | N | 0.392624401 | None | None | N |
| D/F | 0.6159 | likely_pathogenic | 0.6023 | pathogenic | -0.238 | Destabilizing | 0.791 | D | 0.391 | neutral | None | None | None | None | N |
| D/G | 0.1417 | likely_benign | 0.1488 | benign | -0.932 | Destabilizing | 0.027 | N | 0.316 | neutral | N | 0.480746741 | None | None | N |
| D/H | 0.2691 | likely_benign | 0.2563 | benign | -0.318 | Destabilizing | 0.484 | N | 0.335 | neutral | N | 0.477939025 | None | None | N |
| D/I | 0.3435 | ambiguous | 0.3346 | benign | 0.137 | Stabilizing | 0.38 | N | 0.393 | neutral | None | None | None | None | N |
| D/K | 0.2695 | likely_benign | 0.2529 | benign | -0.181 | Destabilizing | 0.081 | N | 0.305 | neutral | None | None | None | None | N |
| D/L | 0.3551 | ambiguous | 0.3458 | ambiguous | 0.137 | Stabilizing | 0.149 | N | 0.312 | neutral | None | None | None | None | N |
| D/M | 0.5114 | ambiguous | 0.4931 | ambiguous | 0.422 | Stabilizing | 0.935 | D | 0.365 | neutral | None | None | None | None | N |
| D/N | 0.0922 | likely_benign | 0.096 | benign | -0.624 | Destabilizing | 0.117 | N | 0.28 | neutral | N | 0.475575691 | None | None | N |
| D/P | 0.8733 | likely_pathogenic | 0.8857 | pathogenic | -0.097 | Destabilizing | 0.262 | N | 0.371 | neutral | None | None | None | None | N |
| D/Q | 0.203 | likely_benign | 0.1962 | benign | -0.538 | Destabilizing | 0.081 | N | 0.325 | neutral | None | None | None | None | N |
| D/R | 0.3209 | likely_benign | 0.3068 | benign | 0.074 | Stabilizing | 0.235 | N | 0.377 | neutral | None | None | None | None | N |
| D/S | 0.1275 | likely_benign | 0.1229 | benign | -0.81 | Destabilizing | 0.003 | N | 0.105 | neutral | None | None | None | None | N |
| D/T | 0.1995 | likely_benign | 0.1965 | benign | -0.571 | Destabilizing | 0.002 | N | 0.162 | neutral | None | None | None | None | N |
| D/V | 0.1984 | likely_benign | 0.1952 | benign | -0.097 | Destabilizing | 0.117 | N | 0.319 | neutral | N | 0.424570011 | None | None | N |
| D/W | 0.8527 | likely_pathogenic | 0.8436 | pathogenic | 0.009 | Stabilizing | 0.935 | D | 0.47 | neutral | None | None | None | None | N |
| D/Y | 0.2785 | likely_benign | 0.2646 | benign | 0.019 | Stabilizing | 0.741 | D | 0.381 | neutral | N | 0.476661066 | 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.