Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29393 | 88402;88403;88404 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| N2AB | 27752 | 83479;83480;83481 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| N2A | 26825 | 80698;80699;80700 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| N2B | 20328 | 61207;61208;61209 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| Novex-1 | 20453 | 61582;61583;61584 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| Novex-2 | 20520 | 61783;61784;61785 | chr2:178556977;178556976;178556975 | chr2:179421704;179421703;179421702 |
| 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 | rs746109021  |
0.31 | 0.994 | N | 0.527 | 0.39 | 0.399740851666 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs746109021 |
0.31 | 0.994 | N | 0.527 | 0.39 | 0.399740851666 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | N | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs746109021 |
-1.178 | 0.775 | N | 0.571 | 0.242 | 0.156986980423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs746109021 |
-1.178 | 0.775 | N | 0.571 | 0.242 | 0.156986980423 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1224 | likely_benign | 0.1125 | benign | -0.834 | Destabilizing | 0.948 | D | 0.515 | neutral | N | 0.490146786 | None | None | N |
| T/C | 0.3346 | likely_benign | 0.3407 | ambiguous | -0.48 | Destabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | N |
| T/D | 0.5403 | ambiguous | 0.4692 | ambiguous | -0.603 | Destabilizing | 0.998 | D | 0.534 | neutral | None | None | None | None | N |
| T/E | 0.3589 | ambiguous | 0.3147 | benign | -0.449 | Destabilizing | 0.998 | D | 0.533 | neutral | None | None | None | None | N |
| T/F | 0.5303 | ambiguous | 0.4442 | ambiguous | -0.67 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | N |
| T/G | 0.3049 | likely_benign | 0.2799 | benign | -1.214 | Destabilizing | 0.992 | D | 0.541 | neutral | None | None | None | None | N |
| T/H | 0.3202 | likely_benign | 0.2778 | benign | -1.289 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/I | 0.3733 | ambiguous | 0.3153 | benign | 0.139 | Stabilizing | 0.994 | D | 0.527 | neutral | N | 0.505288527 | None | None | N |
| T/K | 0.1582 | likely_benign | 0.1454 | benign | -0.288 | Destabilizing | 0.998 | D | 0.528 | neutral | None | None | None | None | N |
| T/L | 0.1021 | likely_benign | 0.0984 | benign | 0.139 | Stabilizing | 0.269 | N | 0.452 | neutral | None | None | None | None | N |
| T/M | 0.0878 | likely_benign | 0.0833 | benign | 0.049 | Stabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | N |
| T/N | 0.0964 | likely_benign | 0.086 | benign | -0.799 | Destabilizing | 0.997 | D | 0.492 | neutral | N | 0.495500368 | None | None | N |
| T/P | 0.1083 | likely_benign | 0.0927 | benign | -0.153 | Destabilizing | 0.998 | D | 0.557 | neutral | N | 0.466522349 | None | None | N |
| T/Q | 0.1904 | likely_benign | 0.1755 | benign | -0.636 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | N |
| T/R | 0.1423 | likely_benign | 0.1283 | benign | -0.39 | Destabilizing | 0.999 | D | 0.558 | neutral | None | None | None | None | N |
| T/S | 0.158 | likely_benign | 0.1371 | benign | -1.089 | Destabilizing | 0.775 | D | 0.571 | neutral | N | 0.474814008 | None | None | N |
| T/V | 0.268 | likely_benign | 0.2389 | benign | -0.153 | Destabilizing | 0.983 | D | 0.501 | neutral | None | None | None | None | N |
| T/W | 0.8149 | likely_pathogenic | 0.7624 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/Y | 0.4277 | ambiguous | 0.3652 | ambiguous | -0.394 | Destabilizing | 1.0 | D | 0.663 | 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.