Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14549 | 43870;43871;43872 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| N2AB | 12908 | 38947;38948;38949 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| N2A | 11981 | 36166;36167;36168 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| N2B | 5484 | 16675;16676;16677 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| Novex-1 | 5609 | 17050;17051;17052 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| Novex-2 | 5676 | 17251;17252;17253 | chr2:178632249;178632248;178632247 | chr2:179496976;179496975;179496974 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs775953090  |
-0.49 | 0.032 | N | 0.259 | 0.139 | 0.44770609447 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.19E-06 | 0 |
| K/R | rs775953090 |
-0.49 | 0.032 | N | 0.259 | 0.139 | 0.44770609447 | gnomAD-4.0.0 | 1.37305E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80272E-06 | 0 | 0 |
| K/T | rs775953090 |
-0.635 | 0.942 | D | 0.616 | 0.291 | None | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 6.85E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/T | rs775953090 |
-0.635 | 0.942 | D | 0.616 | 0.291 | None | gnomAD-4.0.0 | 1.37305E-06 | None | None | None | None | N | None | 5.99018E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7574 | likely_pathogenic | 0.6964 | pathogenic | -0.666 | Destabilizing | 0.754 | D | 0.594 | neutral | None | None | None | None | N |
| K/C | 0.9085 | likely_pathogenic | 0.8936 | pathogenic | -0.776 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/D | 0.8526 | likely_pathogenic | 0.816 | pathogenic | -0.544 | Destabilizing | 0.754 | D | 0.613 | neutral | None | None | None | None | N |
| K/E | 0.436 | ambiguous | 0.3792 | ambiguous | -0.424 | Destabilizing | 0.014 | N | 0.303 | neutral | D | 0.61333872 | None | None | N |
| K/F | 0.9301 | likely_pathogenic | 0.9078 | pathogenic | -0.377 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| K/G | 0.7716 | likely_pathogenic | 0.7244 | pathogenic | -1.05 | Destabilizing | 0.86 | D | 0.652 | neutral | None | None | None | None | N |
| K/H | 0.643 | likely_pathogenic | 0.5846 | pathogenic | -1.435 | Destabilizing | 0.994 | D | 0.643 | neutral | None | None | None | None | N |
| K/I | 0.6918 | likely_pathogenic | 0.629 | pathogenic | 0.335 | Stabilizing | 0.971 | D | 0.737 | prob.delet. | D | 0.660008444 | None | None | N |
| K/L | 0.6299 | likely_pathogenic | 0.5821 | pathogenic | 0.335 | Stabilizing | 0.956 | D | 0.649 | neutral | None | None | None | None | N |
| K/M | 0.4169 | ambiguous | 0.3625 | ambiguous | 0.309 | Stabilizing | 0.998 | D | 0.645 | neutral | None | None | None | None | N |
| K/N | 0.6175 | likely_pathogenic | 0.5595 | ambiguous | -0.757 | Destabilizing | 0.942 | D | 0.612 | neutral | D | 0.613468549 | None | None | N |
| K/P | 0.9172 | likely_pathogenic | 0.8885 | pathogenic | 0.031 | Stabilizing | 0.978 | D | 0.671 | neutral | None | None | None | None | N |
| K/Q | 0.3108 | likely_benign | 0.2581 | benign | -0.843 | Destabilizing | 0.89 | D | 0.618 | neutral | D | 0.655717321 | None | None | N |
| K/R | 0.1099 | likely_benign | 0.1003 | benign | -0.77 | Destabilizing | 0.032 | N | 0.259 | neutral | N | 0.509609052 | None | None | N |
| K/S | 0.7676 | likely_pathogenic | 0.7116 | pathogenic | -1.394 | Destabilizing | 0.754 | D | 0.59 | neutral | None | None | None | None | N |
| K/T | 0.4548 | ambiguous | 0.3675 | ambiguous | -1.061 | Destabilizing | 0.942 | D | 0.616 | neutral | D | 0.535519457 | None | None | N |
| K/V | 0.6887 | likely_pathogenic | 0.6324 | pathogenic | 0.031 | Stabilizing | 0.956 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/W | 0.9384 | likely_pathogenic | 0.9177 | pathogenic | -0.268 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| K/Y | 0.8598 | likely_pathogenic | 0.8314 | pathogenic | 0.054 | Stabilizing | 0.993 | D | 0.711 | prob.delet. | 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.