Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35171 | 105736;105737;105738 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| N2AB | 33530 | 100813;100814;100815 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| N2A | 32603 | 98032;98033;98034 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| N2B | 26106 | 78541;78542;78543 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| Novex-1 | 26231 | 78916;78917;78918 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| Novex-2 | 26298 | 79117;79118;79119 | chr2:178531104;178531103;178531102 | chr2:179395831;179395830;179395829 |
| 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/I | rs774524898  |
-0.299 | 0.004 | N | 0.297 | 0.254 | None | gnomAD-2.1.1 | 1.64534E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.11104E-03 | None | 0 | 6.2E-05 | 0 |
| T/I | rs774524898 |
-0.299 | 0.004 | N | 0.297 | 0.254 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 1.24327E-03 | 0 |
| T/I | rs774524898 |
-0.299 | 0.004 | N | 0.297 | 0.254 | None | gnomAD-4.0.0 | 1.01619E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.28731E-04 | 5.00049E-05 | 1.08691E-03 | 6.40369E-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 | 0.0714 | likely_benign | 0.0667 | benign | -0.314 | Destabilizing | None | N | 0.098 | neutral | N | 0.449267512 | None | None | N |
| T/C | 0.4434 | ambiguous | 0.3904 | ambiguous | -0.185 | Destabilizing | 0.177 | N | 0.317 | neutral | None | None | None | None | N |
| T/D | 0.2645 | likely_benign | 0.2313 | benign | 0.211 | Stabilizing | 0.029 | N | 0.315 | neutral | None | None | None | None | N |
| T/E | 0.2355 | likely_benign | 0.2032 | benign | 0.122 | Stabilizing | 0.015 | N | 0.297 | neutral | None | None | None | None | N |
| T/F | 0.2124 | likely_benign | 0.1881 | benign | -0.924 | Destabilizing | 0.096 | N | 0.339 | neutral | None | None | None | None | N |
| T/G | 0.1837 | likely_benign | 0.1647 | benign | -0.406 | Destabilizing | 0.006 | N | 0.265 | neutral | None | None | None | None | N |
| T/H | 0.2123 | likely_benign | 0.1798 | benign | -0.759 | Destabilizing | 0.177 | N | 0.307 | neutral | None | None | None | None | N |
| T/I | 0.1659 | likely_benign | 0.1464 | benign | -0.196 | Destabilizing | 0.004 | N | 0.297 | neutral | N | 0.486555384 | None | None | N |
| T/K | 0.184 | likely_benign | 0.1549 | benign | -0.241 | Destabilizing | 0.015 | N | 0.295 | neutral | None | None | None | None | N |
| T/L | 0.1076 | likely_benign | 0.1009 | benign | -0.196 | Destabilizing | 0.006 | N | 0.285 | neutral | None | None | None | None | N |
| T/M | 0.1135 | likely_benign | 0.1069 | benign | 0.032 | Stabilizing | 0.096 | N | 0.316 | neutral | None | None | None | None | N |
| T/N | 0.1 | likely_benign | 0.0905 | benign | -0.007 | Destabilizing | 0.011 | N | 0.155 | neutral | N | 0.501235127 | None | None | N |
| T/P | 0.0873 | likely_benign | 0.0834 | benign | -0.209 | Destabilizing | 0.044 | N | 0.358 | neutral | N | 0.468565348 | None | None | N |
| T/Q | 0.1949 | likely_benign | 0.1711 | benign | -0.247 | Destabilizing | 0.096 | N | 0.359 | neutral | None | None | None | None | N |
| T/R | 0.1411 | likely_benign | 0.1209 | benign | -0.019 | Destabilizing | 0.029 | N | 0.377 | neutral | None | None | None | None | N |
| T/S | 0.0847 | likely_benign | 0.079 | benign | -0.204 | Destabilizing | None | N | 0.14 | neutral | N | 0.411015768 | None | None | N |
| T/V | 0.1336 | likely_benign | 0.1202 | benign | -0.209 | Destabilizing | None | N | 0.091 | neutral | None | None | None | None | N |
| T/W | 0.5754 | likely_pathogenic | 0.5148 | ambiguous | -0.948 | Destabilizing | 0.712 | D | 0.321 | neutral | None | None | None | None | N |
| T/Y | 0.2556 | likely_benign | 0.224 | benign | -0.644 | Destabilizing | 0.177 | N | 0.328 | 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.