Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25957 | 78094;78095;78096 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| N2AB | 24316 | 73171;73172;73173 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| N2A | 23389 | 70390;70391;70392 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| N2B | 16892 | 50899;50900;50901 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| Novex-1 | 17017 | 51274;51275;51276 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| Novex-2 | 17084 | 51475;51476;51477 | chr2:178568263;178568262;178568261 | chr2:179432990;179432989;179432988 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs372165943  |
-0.149 | 0.97 | N | 0.463 | 0.409 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs372165943 |
-0.149 | 0.97 | N | 0.463 | 0.409 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs372165943 |
-0.149 | 0.97 | N | 0.463 | 0.409 | None | gnomAD-4.0.0 | 3.84461E-06 | None | None | None | None | N | None | 5.07717E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1077 | likely_benign | 0.0996 | benign | -0.525 | Destabilizing | 0.656 | D | 0.437 | neutral | N | 0.430166384 | None | None | N |
| T/C | 0.5553 | ambiguous | 0.4783 | ambiguous | -0.293 | Destabilizing | 0.998 | D | 0.502 | neutral | None | None | None | None | N |
| T/D | 0.6503 | likely_pathogenic | 0.6305 | pathogenic | -0.107 | Destabilizing | 0.754 | D | 0.444 | neutral | None | None | None | None | N |
| T/E | 0.4115 | ambiguous | 0.3896 | ambiguous | -0.18 | Destabilizing | 0.019 | N | 0.279 | neutral | None | None | None | None | N |
| T/F | 0.4751 | ambiguous | 0.4358 | ambiguous | -0.943 | Destabilizing | 0.993 | D | 0.589 | neutral | None | None | None | None | N |
| T/G | 0.4098 | ambiguous | 0.3775 | ambiguous | -0.676 | Destabilizing | 0.86 | D | 0.481 | neutral | None | None | None | None | N |
| T/H | 0.3986 | ambiguous | 0.3599 | ambiguous | -1.004 | Destabilizing | 0.994 | D | 0.593 | neutral | None | None | None | None | N |
| T/I | 0.2775 | likely_benign | 0.2323 | benign | -0.239 | Destabilizing | 0.97 | D | 0.463 | neutral | N | 0.499471754 | None | None | N |
| T/K | 0.2454 | likely_benign | 0.2132 | benign | -0.529 | Destabilizing | 0.076 | N | 0.276 | neutral | None | None | None | None | N |
| T/L | 0.1488 | likely_benign | 0.1311 | benign | -0.239 | Destabilizing | 0.86 | D | 0.447 | neutral | None | None | None | None | N |
| T/M | 0.1018 | likely_benign | 0.0914 | benign | 0.086 | Stabilizing | 0.998 | D | 0.473 | neutral | None | None | None | None | N |
| T/N | 0.1984 | likely_benign | 0.1775 | benign | -0.311 | Destabilizing | 0.942 | D | 0.472 | neutral | N | 0.475882818 | None | None | N |
| T/P | 0.1319 | likely_benign | 0.1297 | benign | -0.305 | Destabilizing | 0.97 | D | 0.468 | neutral | N | 0.390442055 | None | None | N |
| T/Q | 0.2836 | likely_benign | 0.2463 | benign | -0.594 | Destabilizing | 0.915 | D | 0.464 | neutral | None | None | None | None | N |
| T/R | 0.232 | likely_benign | 0.2062 | benign | -0.194 | Destabilizing | 0.915 | D | 0.431 | neutral | None | None | None | None | N |
| T/S | 0.1899 | likely_benign | 0.1789 | benign | -0.519 | Destabilizing | 0.822 | D | 0.457 | neutral | N | 0.473823948 | None | None | N |
| T/V | 0.1971 | likely_benign | 0.1669 | benign | -0.305 | Destabilizing | 0.926 | D | 0.482 | neutral | None | None | None | None | N |
| T/W | 0.788 | likely_pathogenic | 0.7645 | pathogenic | -0.901 | Destabilizing | 0.998 | D | 0.61 | neutral | None | None | None | None | N |
| T/Y | 0.4655 | ambiguous | 0.4243 | ambiguous | -0.649 | Destabilizing | 0.993 | D | 0.591 | 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.