Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35161 | 105706;105707;105708 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| N2AB | 33520 | 100783;100784;100785 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| N2A | 32593 | 98002;98003;98004 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| N2B | 26096 | 78511;78512;78513 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| Novex-1 | 26221 | 78886;78887;78888 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| Novex-2 | 26288 | 79087;79088;79089 | chr2:178531134;178531133;178531132 | chr2:179395861;179395860;179395859 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs764804165  |
-0.568 | 0.552 | N | 0.549 | 0.202 | 0.241664281697 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs764804165 |
-0.568 | 0.552 | N | 0.549 | 0.202 | 0.241664281697 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21507E-04 | 0 |
| T/N | rs372263729 |
-0.418 | 0.954 | N | 0.555 | 0.33 | None | gnomAD-2.1.1 | 4.63E-05 | None | None | None | None | N | None | 5.37501E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/N | rs372263729 |
-0.418 | 0.954 | N | 0.555 | 0.33 | None | gnomAD-3.1.2 | 1.70913E-04 | None | None | None | None | N | None | 6.27655E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs372263729 |
-0.418 | 0.954 | N | 0.555 | 0.33 | None | gnomAD-4.0.0 | 3.22217E-05 | None | None | None | None | N | None | 6.40837E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47542E-07 | 0 | 4.80246E-05 |
| T/S | rs764804165 |
None | 0.189 | N | 0.483 | 0.129 | 0.151104730317 | 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 |
| T/S | rs764804165 |
None | 0.189 | N | 0.483 | 0.129 | 0.151104730317 | gnomAD-4.0.0 | 6.84137E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65634E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1172 | likely_benign | 0.1155 | benign | -0.826 | Destabilizing | 0.552 | D | 0.549 | neutral | N | 0.51378035 | None | None | N |
| T/C | 0.4635 | ambiguous | 0.4642 | ambiguous | -0.512 | Destabilizing | 0.998 | D | 0.642 | neutral | None | None | None | None | N |
| T/D | 0.5211 | ambiguous | 0.5123 | ambiguous | -0.311 | Destabilizing | 0.965 | D | 0.621 | neutral | None | None | None | None | N |
| T/E | 0.3522 | ambiguous | 0.3461 | ambiguous | -0.215 | Destabilizing | 0.965 | D | 0.62 | neutral | None | None | None | None | N |
| T/F | 0.224 | likely_benign | 0.2329 | benign | -0.587 | Destabilizing | 0.965 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/G | 0.4151 | ambiguous | 0.3973 | ambiguous | -1.175 | Destabilizing | 0.888 | D | 0.626 | neutral | None | None | None | None | N |
| T/H | 0.219 | likely_benign | 0.214 | benign | -1.305 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/I | 0.107 | likely_benign | 0.1199 | benign | 0.045 | Stabilizing | 0.041 | N | 0.427 | neutral | D | 0.527019006 | None | None | N |
| T/K | 0.1704 | likely_benign | 0.1664 | benign | -0.575 | Destabilizing | 0.965 | D | 0.621 | neutral | None | None | None | None | N |
| T/L | 0.1047 | likely_benign | 0.1045 | benign | 0.045 | Stabilizing | 0.798 | D | 0.545 | neutral | None | None | None | None | N |
| T/M | 0.0967 | likely_benign | 0.1014 | benign | 0.059 | Stabilizing | 0.991 | D | 0.658 | neutral | None | None | None | None | N |
| T/N | 0.1596 | likely_benign | 0.1541 | benign | -0.807 | Destabilizing | 0.954 | D | 0.555 | neutral | N | 0.511015968 | None | None | N |
| T/P | 0.6318 | likely_pathogenic | 0.6118 | pathogenic | -0.211 | Destabilizing | 0.977 | D | 0.657 | neutral | D | 0.543870343 | None | None | N |
| T/Q | 0.2135 | likely_benign | 0.2036 | benign | -0.758 | Destabilizing | 0.983 | D | 0.666 | neutral | None | None | None | None | N |
| T/R | 0.1218 | likely_benign | 0.1225 | benign | -0.543 | Destabilizing | 0.983 | D | 0.653 | neutral | None | None | None | None | N |
| T/S | 0.1442 | likely_benign | 0.1351 | benign | -1.109 | Destabilizing | 0.189 | N | 0.483 | neutral | N | 0.490380628 | None | None | N |
| T/V | 0.1203 | likely_benign | 0.1195 | benign | -0.211 | Destabilizing | 0.577 | D | 0.543 | neutral | None | None | None | None | N |
| T/W | 0.5668 | likely_pathogenic | 0.5834 | pathogenic | -0.612 | Destabilizing | 0.998 | D | 0.668 | neutral | None | None | None | None | N |
| T/Y | 0.2839 | likely_benign | 0.2775 | benign | -0.317 | Destabilizing | 0.983 | D | 0.701 | prob.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.