Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17272 | 52039;52040;52041 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| N2AB | 15631 | 47116;47117;47118 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| N2A | 14704 | 44335;44336;44337 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| N2B | 8207 | 24844;24845;24846 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| Novex-1 | 8332 | 25219;25220;25221 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| Novex-2 | 8399 | 25420;25421;25422 | chr2:178609496;178609495;178609494 | chr2:179474223;179474222;179474221 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | rs1308609622  |
-0.339 | 0.656 | N | 0.371 | 0.24 | 0.298745278005 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| S/A | rs1308609622 |
-0.339 | 0.656 | N | 0.371 | 0.24 | 0.298745278005 | gnomAD-4.0.0 | 6.16231E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.04457E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1177 | likely_benign | 0.1179 | benign | -0.226 | Destabilizing | 0.656 | D | 0.371 | neutral | N | 0.513953708 | None | None | I |
| S/C | 0.172 | likely_benign | 0.1733 | benign | -0.476 | Destabilizing | 0.997 | D | 0.644 | neutral | N | 0.506042445 | None | None | I |
| S/D | 0.7284 | likely_pathogenic | 0.7068 | pathogenic | 0.311 | Stabilizing | 0.993 | D | 0.527 | neutral | None | None | None | None | I |
| S/E | 0.6856 | likely_pathogenic | 0.6747 | pathogenic | 0.237 | Stabilizing | 0.974 | D | 0.52 | neutral | None | None | None | None | I |
| S/F | 0.2231 | likely_benign | 0.223 | benign | -0.945 | Destabilizing | 0.032 | N | 0.257 | neutral | N | 0.494179161 | None | None | I |
| S/G | 0.1983 | likely_benign | 0.199 | benign | -0.304 | Destabilizing | 0.926 | D | 0.411 | neutral | None | None | None | None | I |
| S/H | 0.4385 | ambiguous | 0.4257 | ambiguous | -0.566 | Destabilizing | 0.998 | D | 0.654 | neutral | None | None | None | None | I |
| S/I | 0.254 | likely_benign | 0.2556 | benign | -0.148 | Destabilizing | 0.915 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/K | 0.7935 | likely_pathogenic | 0.7818 | pathogenic | -0.259 | Destabilizing | 0.926 | D | 0.522 | neutral | None | None | None | None | I |
| S/L | 0.1353 | likely_benign | 0.1427 | benign | -0.148 | Destabilizing | 0.754 | D | 0.553 | neutral | None | None | None | None | I |
| S/M | 0.2412 | likely_benign | 0.2463 | benign | -0.312 | Destabilizing | 0.994 | D | 0.656 | neutral | None | None | None | None | I |
| S/N | 0.3529 | ambiguous | 0.3484 | ambiguous | -0.163 | Destabilizing | 0.993 | D | 0.55 | neutral | None | None | None | None | I |
| S/P | 0.9658 | likely_pathogenic | 0.964 | pathogenic | -0.148 | Destabilizing | 0.99 | D | 0.681 | prob.neutral | N | 0.505535466 | None | None | I |
| S/Q | 0.6085 | likely_pathogenic | 0.5941 | pathogenic | -0.289 | Destabilizing | 0.993 | D | 0.577 | neutral | None | None | None | None | I |
| S/R | 0.7106 | likely_pathogenic | 0.6971 | pathogenic | -0.066 | Destabilizing | 0.978 | D | 0.681 | prob.neutral | None | None | None | None | I |
| S/T | 0.0909 | likely_benign | 0.0933 | benign | -0.236 | Destabilizing | 0.904 | D | 0.398 | neutral | N | 0.492076926 | None | None | I |
| S/V | 0.267 | likely_benign | 0.2703 | benign | -0.148 | Destabilizing | 0.915 | D | 0.611 | neutral | None | None | None | None | I |
| S/W | 0.4205 | ambiguous | 0.4059 | ambiguous | -1.044 | Destabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | I |
| S/Y | 0.2533 | likely_benign | 0.2426 | benign | -0.694 | Destabilizing | 0.89 | D | 0.698 | prob.neutral | N | 0.516891771 | 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.