Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20816 | 62671;62672;62673 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| N2AB | 19175 | 57748;57749;57750 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| N2A | 18248 | 54967;54968;54969 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| N2B | 11751 | 35476;35477;35478 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| Novex-1 | 11876 | 35851;35852;35853 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| Novex-2 | 11943 | 36052;36053;36054 | chr2:178589279;178589278;178589277 | chr2:179454006;179454005;179454004 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.999 | N | 0.637 | 0.394 | 0.369867359543 | gnomAD-4.0.0 | 6.84343E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.657E-05 |
| P/R | rs376951521  |
0.167 | 0.999 | N | 0.647 | 0.376 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 2.0668E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs376951521 |
0.167 | 0.999 | N | 0.647 | 0.376 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 1.68894E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs376951521 |
0.167 | 0.999 | N | 0.647 | 0.376 | None | gnomAD-4.0.0 | 6.1985E-06 | None | None | None | None | N | None | 1.33504E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.108 | likely_benign | 0.1184 | benign | -0.421 | Destabilizing | 0.996 | D | 0.548 | neutral | N | 0.427752436 | None | None | N |
| P/C | 0.6668 | likely_pathogenic | 0.7557 | pathogenic | -0.858 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| P/D | 0.4619 | ambiguous | 0.5449 | ambiguous | -0.404 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/E | 0.3221 | likely_benign | 0.3832 | ambiguous | -0.523 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| P/F | 0.6465 | likely_pathogenic | 0.7118 | pathogenic | -0.766 | Destabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | N |
| P/G | 0.3091 | likely_benign | 0.3693 | ambiguous | -0.481 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | N |
| P/H | 0.2996 | likely_benign | 0.3723 | ambiguous | -0.037 | Destabilizing | 1.0 | D | 0.618 | neutral | None | None | None | None | N |
| P/I | 0.4186 | ambiguous | 0.479 | ambiguous | -0.407 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| P/K | 0.4077 | ambiguous | 0.5301 | ambiguous | -0.468 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| P/L | 0.1748 | likely_benign | 0.2028 | benign | -0.407 | Destabilizing | 0.999 | D | 0.637 | neutral | N | 0.467214901 | None | None | N |
| P/M | 0.3838 | ambiguous | 0.4363 | ambiguous | -0.61 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| P/N | 0.3532 | ambiguous | 0.4169 | ambiguous | -0.297 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | N |
| P/Q | 0.1926 | likely_benign | 0.239 | benign | -0.518 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.439316224 | None | None | N |
| P/R | 0.3405 | ambiguous | 0.4349 | ambiguous | 0.019 | Stabilizing | 0.999 | D | 0.647 | neutral | N | 0.411494905 | None | None | N |
| P/S | 0.1361 | likely_benign | 0.1572 | benign | -0.604 | Destabilizing | 0.998 | D | 0.631 | neutral | N | 0.385865741 | None | None | N |
| P/T | 0.1436 | likely_benign | 0.1664 | benign | -0.633 | Destabilizing | 0.884 | D | 0.335 | neutral | N | 0.439316224 | None | None | N |
| P/V | 0.2683 | likely_benign | 0.3145 | benign | -0.384 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| P/W | 0.7762 | likely_pathogenic | 0.8394 | pathogenic | -0.81 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| P/Y | 0.5958 | likely_pathogenic | 0.6814 | pathogenic | -0.551 | Destabilizing | 1.0 | D | 0.657 | 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.