Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33563 | 100912;100913;100914 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| N2AB | 31922 | 95989;95990;95991 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| N2A | 30995 | 93208;93209;93210 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| N2B | 24498 | 73717;73718;73719 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| Novex-1 | 24623 | 74092;74093;74094 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| Novex-2 | 24690 | 74293;74294;74295 | chr2:178536060;178536059;178536058 | chr2:179400787;179400786;179400785 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs1691369935  |
None | 0.637 | N | 0.384 | 0.342 | 0.29527378943 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/G | rs1691369935 |
None | 0.637 | N | 0.384 | 0.342 | 0.29527378943 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4702E-05 | 0 | 0 |
| D/N | rs746118157 |
0.759 | 0.006 | N | 0.184 | 0.234 | 0.212008924253 | gnomAD-2.1.1 | 4.14E-06 | None | None | None | None | N | None | 0 | 2.94E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs746118157 |
0.759 | 0.006 | N | 0.184 | 0.234 | 0.212008924253 | gnomAD-4.0.0 | 3.25247E-06 | None | None | None | None | N | None | 0 | 2.31664E-05 | None | 0 | 0 | None | 0 | 0 | 2.93071E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1681 | likely_benign | 0.1701 | benign | -0.083 | Destabilizing | 0.708 | D | 0.395 | neutral | N | 0.472587088 | None | None | N |
| D/C | 0.7317 | likely_pathogenic | 0.7798 | pathogenic | 0.442 | Stabilizing | 0.987 | D | 0.431 | neutral | None | None | None | None | N |
| D/E | 0.1161 | likely_benign | 0.1395 | benign | -0.19 | Destabilizing | 0.004 | N | 0.251 | neutral | N | 0.397742613 | None | None | N |
| D/F | 0.723 | likely_pathogenic | 0.7563 | pathogenic | -0.417 | Destabilizing | 0.996 | D | 0.399 | neutral | None | None | None | None | N |
| D/G | 0.2285 | likely_benign | 0.2381 | benign | -0.217 | Destabilizing | 0.637 | D | 0.384 | neutral | N | 0.489154051 | None | None | N |
| D/H | 0.3985 | ambiguous | 0.4216 | ambiguous | -0.335 | Destabilizing | 0.959 | D | 0.35 | neutral | N | 0.505643656 | None | None | N |
| D/I | 0.4254 | ambiguous | 0.4583 | ambiguous | 0.203 | Stabilizing | 0.976 | D | 0.411 | neutral | None | None | None | None | N |
| D/K | 0.3932 | ambiguous | 0.3839 | ambiguous | 0.571 | Stabilizing | 0.92 | D | 0.355 | neutral | None | None | None | None | N |
| D/L | 0.4758 | ambiguous | 0.5138 | ambiguous | 0.203 | Stabilizing | 0.976 | D | 0.39 | neutral | None | None | None | None | N |
| D/M | 0.621 | likely_pathogenic | 0.6673 | pathogenic | 0.472 | Stabilizing | 0.997 | D | 0.394 | neutral | None | None | None | None | N |
| D/N | 0.1122 | likely_benign | 0.1197 | benign | 0.519 | Stabilizing | 0.006 | N | 0.184 | neutral | N | 0.466527908 | None | None | N |
| D/P | 0.8741 | likely_pathogenic | 0.8977 | pathogenic | 0.128 | Stabilizing | 0.831 | D | 0.353 | neutral | None | None | None | None | N |
| D/Q | 0.3456 | ambiguous | 0.3611 | ambiguous | 0.493 | Stabilizing | 0.938 | D | 0.337 | neutral | None | None | None | None | N |
| D/R | 0.4772 | ambiguous | 0.4754 | ambiguous | 0.528 | Stabilizing | 0.976 | D | 0.367 | neutral | None | None | None | None | N |
| D/S | 0.1233 | likely_benign | 0.1339 | benign | 0.405 | Stabilizing | 0.399 | N | 0.388 | neutral | None | None | None | None | N |
| D/T | 0.223 | likely_benign | 0.2377 | benign | 0.5 | Stabilizing | 0.019 | N | 0.287 | neutral | None | None | None | None | N |
| D/V | 0.2647 | likely_benign | 0.2908 | benign | 0.128 | Stabilizing | 0.842 | D | 0.39 | neutral | D | 0.533118259 | None | None | N |
| D/W | 0.9317 | likely_pathogenic | 0.9427 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.562 | neutral | None | None | None | None | N |
| D/Y | 0.3896 | ambiguous | 0.4074 | ambiguous | -0.207 | Destabilizing | 0.995 | D | 0.4 | neutral | N | 0.512454985 | 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.