Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33558 | 100897;100898;100899 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| N2AB | 31917 | 95974;95975;95976 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| N2A | 30990 | 93193;93194;93195 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| N2B | 24493 | 73702;73703;73704 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| Novex-1 | 24618 | 74077;74078;74079 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| Novex-2 | 24685 | 74278;74279;74280 | chr2:178536075;178536074;178536073 | chr2:179400802;179400801;179400800 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs376376588  |
None | 0.916 | N | 0.407 | 0.318 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | rs376376588 |
None | 0.916 | N | 0.407 | 0.318 | None | gnomAD-4.0.0 | 3.73275E-06 | None | None | None | None | N | None | 2.67508E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.40277E-06 | 0 | 0 |
| A/S | rs376376588 |
-1.488 | 0.023 | N | 0.362 | 0.045 | 0.220303561663 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| A/S | rs376376588 |
-1.488 | 0.023 | N | 0.362 | 0.045 | 0.220303561663 | gnomAD-4.0.0 | 6.87177E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52423E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5619 | ambiguous | 0.5706 | pathogenic | -1.318 | Destabilizing | 0.982 | D | 0.382 | neutral | None | None | None | None | N |
| A/D | 0.5188 | ambiguous | 0.4605 | ambiguous | -1.519 | Destabilizing | 0.504 | D | 0.441 | neutral | None | None | None | None | N |
| A/E | 0.4875 | ambiguous | 0.4151 | ambiguous | -1.553 | Destabilizing | 0.682 | D | 0.377 | neutral | N | 0.430873752 | None | None | N |
| A/F | 0.5499 | ambiguous | 0.4824 | ambiguous | -1.251 | Destabilizing | 0.982 | D | 0.507 | neutral | None | None | None | None | N |
| A/G | 0.1628 | likely_benign | 0.1698 | benign | -1.324 | Destabilizing | 0.07 | N | 0.307 | neutral | N | 0.481361287 | None | None | N |
| A/H | 0.6017 | likely_pathogenic | 0.5392 | ambiguous | -1.353 | Destabilizing | 0.99 | D | 0.472 | neutral | None | None | None | None | N |
| A/I | 0.4411 | ambiguous | 0.4425 | ambiguous | -0.551 | Destabilizing | 0.792 | D | 0.353 | neutral | None | None | None | None | N |
| A/K | 0.7383 | likely_pathogenic | 0.628 | pathogenic | -1.285 | Destabilizing | 0.792 | D | 0.372 | neutral | None | None | None | None | N |
| A/L | 0.2794 | likely_benign | 0.2669 | benign | -0.551 | Destabilizing | 0.611 | D | 0.374 | neutral | None | None | None | None | N |
| A/M | 0.3394 | likely_benign | 0.3472 | ambiguous | -0.521 | Destabilizing | 0.982 | D | 0.42 | neutral | None | None | None | None | N |
| A/N | 0.2783 | likely_benign | 0.257 | benign | -1.099 | Destabilizing | 0.001 | N | 0.277 | neutral | None | None | None | None | N |
| A/P | 0.5333 | ambiguous | 0.5048 | ambiguous | -0.686 | Destabilizing | 0.916 | D | 0.407 | neutral | N | 0.427412159 | None | None | N |
| A/Q | 0.4461 | ambiguous | 0.3722 | ambiguous | -1.306 | Destabilizing | 0.964 | D | 0.429 | neutral | None | None | None | None | N |
| A/R | 0.6837 | likely_pathogenic | 0.5507 | ambiguous | -0.885 | Destabilizing | 0.964 | D | 0.407 | neutral | None | None | None | None | N |
| A/S | 0.077 | likely_benign | 0.0776 | benign | -1.475 | Destabilizing | 0.023 | N | 0.362 | neutral | N | 0.397587898 | None | None | N |
| A/T | 0.0924 | likely_benign | 0.0935 | benign | -1.414 | Destabilizing | 0.001 | N | 0.084 | neutral | N | 0.410018477 | None | None | N |
| A/V | 0.2312 | likely_benign | 0.2411 | benign | -0.686 | Destabilizing | 0.007 | N | 0.244 | neutral | N | 0.459812579 | None | None | N |
| A/W | 0.9077 | likely_pathogenic | 0.8676 | pathogenic | -1.523 | Destabilizing | 0.998 | D | 0.584 | neutral | None | None | None | None | N |
| A/Y | 0.6634 | likely_pathogenic | 0.6008 | pathogenic | -1.14 | Destabilizing | 0.982 | D | 0.503 | 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.