Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2430 | 7513;7514;7515 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| N2AB | 2430 | 7513;7514;7515 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| N2A | 2430 | 7513;7514;7515 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| N2B | 2384 | 7375;7376;7377 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| Novex-1 | 2384 | 7375;7376;7377 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| Novex-2 | 2384 | 7375;7376;7377 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
| Novex-3 | 2430 | 7513;7514;7515 | chr2:178773880;178773879;178773878 | chr2:179638607;179638606;179638605 |
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 | rs775687221  |
-0.271 | 0.993 | N | 0.609 | 0.361 | 0.750005655083 | gnomAD-2.1.1 | 7.99E-06 | None | None | None | None | I | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs775687221 |
-0.271 | 0.993 | N | 0.609 | 0.361 | 0.750005655083 | gnomAD-4.0.0 | 6.36227E-06 | None | None | None | None | I | None | 0 | 6.85965E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0217E-05 |
| P/S | rs761169279 |
-0.754 | 0.993 | N | 0.477 | 0.425 | 0.346768085243 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs761169279 |
-0.754 | 0.993 | N | 0.477 | 0.425 | 0.346768085243 | gnomAD-4.0.0 | 1.36816E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99308E-07 | 1.15931E-05 | 0 |
| P/T | rs761169279 |
-0.739 | 0.997 | N | 0.501 | 0.45 | 0.499473279415 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | I | None | 0 | 8.47E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs761169279 |
-0.739 | 0.997 | N | 0.501 | 0.45 | 0.499473279415 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.30924E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs761169279 |
-0.739 | 0.997 | N | 0.501 | 0.45 | 0.499473279415 | gnomAD-4.0.0 | 2.47831E-06 | None | None | None | None | I | None | 0 | 6.66756E-05 | 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 | 0.131 | likely_benign | 0.1118 | benign | -0.578 | Destabilizing | 0.977 | D | 0.471 | neutral | N | 0.487046679 | None | None | I |
| P/C | 0.681 | likely_pathogenic | 0.5994 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| P/D | 0.4765 | ambiguous | 0.4101 | ambiguous | -0.26 | Destabilizing | 0.998 | D | 0.555 | neutral | None | None | None | None | I |
| P/E | 0.3526 | ambiguous | 0.3027 | benign | -0.351 | Destabilizing | 0.995 | D | 0.473 | neutral | None | None | None | None | I |
| P/F | 0.6847 | likely_pathogenic | 0.5866 | pathogenic | -0.663 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| P/G | 0.3563 | ambiguous | 0.3128 | benign | -0.739 | Destabilizing | 0.998 | D | 0.468 | neutral | None | None | None | None | I |
| P/H | 0.2639 | likely_benign | 0.2183 | benign | -0.239 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | I |
| P/I | 0.5483 | ambiguous | 0.4542 | ambiguous | -0.298 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | I |
| P/K | 0.3764 | ambiguous | 0.3108 | benign | -0.556 | Destabilizing | 0.966 | D | 0.486 | neutral | None | None | None | None | I |
| P/L | 0.1968 | likely_benign | 0.1628 | benign | -0.298 | Destabilizing | 0.993 | D | 0.609 | neutral | N | 0.495495239 | None | None | I |
| P/M | 0.4885 | ambiguous | 0.4131 | ambiguous | -0.425 | Destabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | I |
| P/N | 0.3789 | ambiguous | 0.3229 | benign | -0.365 | Destabilizing | 0.995 | D | 0.574 | neutral | None | None | None | None | I |
| P/Q | 0.2273 | likely_benign | 0.1915 | benign | -0.567 | Destabilizing | 0.993 | D | 0.533 | neutral | N | 0.493280309 | None | None | I |
| P/R | 0.2547 | likely_benign | 0.2078 | benign | -0.05 | Destabilizing | 0.117 | N | 0.333 | neutral | N | 0.469239612 | None | None | I |
| P/S | 0.151 | likely_benign | 0.1302 | benign | -0.763 | Destabilizing | 0.993 | D | 0.477 | neutral | N | 0.452399193 | None | None | I |
| P/T | 0.1624 | likely_benign | 0.1345 | benign | -0.746 | Destabilizing | 0.997 | D | 0.501 | neutral | N | 0.461328425 | None | None | I |
| P/V | 0.3772 | ambiguous | 0.3087 | benign | -0.356 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | I |
| P/W | 0.8028 | likely_pathogenic | 0.7353 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/Y | 0.6044 | likely_pathogenic | 0.5154 | ambiguous | -0.461 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | 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.