Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21180 | 63763;63764;63765 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| N2AB | 19539 | 58840;58841;58842 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| N2A | 18612 | 56059;56060;56061 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| N2B | 12115 | 36568;36569;36570 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| Novex-1 | 12240 | 36943;36944;36945 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| Novex-2 | 12307 | 37144;37145;37146 | chr2:178587771;178587770;178587769 | chr2:179452498;179452497;179452496 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs774558749  |
-0.089 | 0.491 | D | 0.388 | 0.35 | 0.640709723699 | gnomAD-4.0.0 | 3.2228E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.89764E-06 | 1.4529E-05 | 0 |
| M/L | rs2049352693 |
None | None | N | 0.153 | 0.184 | 0.401753679984 | gnomAD-4.0.0 | 7.56728E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.28996E-04 | 0 |
| M/T | rs774558749 |
-0.333 | 0.001 | N | 0.261 | 0.28 | 0.741590790702 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.1E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8068 | likely_pathogenic | 0.8271 | pathogenic | -1.932 | Destabilizing | 0.103 | N | 0.333 | neutral | None | None | None | None | N |
| M/C | 0.8531 | likely_pathogenic | 0.8613 | pathogenic | -1.344 | Destabilizing | 0.965 | D | 0.456 | neutral | None | None | None | None | N |
| M/D | 0.989 | likely_pathogenic | 0.9889 | pathogenic | -0.493 | Destabilizing | 0.561 | D | 0.466 | neutral | None | None | None | None | N |
| M/E | 0.9446 | likely_pathogenic | 0.9441 | pathogenic | -0.401 | Destabilizing | 0.561 | D | 0.389 | neutral | None | None | None | None | N |
| M/F | 0.6431 | likely_pathogenic | 0.6484 | pathogenic | -0.728 | Destabilizing | 0.561 | D | 0.361 | neutral | None | None | None | None | N |
| M/G | 0.921 | likely_pathogenic | 0.9249 | pathogenic | -2.316 | Highly Destabilizing | 0.561 | D | 0.411 | neutral | None | None | None | None | N |
| M/H | 0.9262 | likely_pathogenic | 0.932 | pathogenic | -1.489 | Destabilizing | 0.965 | D | 0.453 | neutral | None | None | None | None | N |
| M/I | 0.7344 | likely_pathogenic | 0.7706 | pathogenic | -0.902 | Destabilizing | 0.001 | N | 0.227 | neutral | N | 0.429753457 | None | None | N |
| M/K | 0.8409 | likely_pathogenic | 0.8542 | pathogenic | -0.655 | Destabilizing | 0.491 | N | 0.388 | neutral | D | 0.530397667 | None | None | N |
| M/L | 0.1118 | likely_benign | 0.1316 | benign | -0.902 | Destabilizing | None | N | 0.153 | neutral | N | 0.335608358 | None | None | N |
| M/N | 0.9223 | likely_pathogenic | 0.9268 | pathogenic | -0.607 | Destabilizing | 0.561 | D | 0.45 | neutral | None | None | None | None | N |
| M/P | 0.977 | likely_pathogenic | 0.9826 | pathogenic | -1.219 | Destabilizing | 0.722 | D | 0.488 | neutral | None | None | None | None | N |
| M/Q | 0.7313 | likely_pathogenic | 0.7229 | pathogenic | -0.551 | Destabilizing | 0.722 | D | 0.463 | neutral | None | None | None | None | N |
| M/R | 0.866 | likely_pathogenic | 0.8724 | pathogenic | -0.391 | Destabilizing | 0.491 | N | 0.443 | neutral | N | 0.512158623 | None | None | N |
| M/S | 0.8404 | likely_pathogenic | 0.8443 | pathogenic | -1.301 | Destabilizing | 0.209 | N | 0.381 | neutral | None | None | None | None | N |
| M/T | 0.6923 | likely_pathogenic | 0.7196 | pathogenic | -1.082 | Destabilizing | 0.001 | N | 0.261 | neutral | N | 0.481662358 | None | None | N |
| M/V | 0.2079 | likely_benign | 0.2303 | benign | -1.219 | Destabilizing | 0.036 | N | 0.301 | neutral | N | 0.492706071 | None | None | N |
| M/W | 0.9211 | likely_pathogenic | 0.9247 | pathogenic | -0.734 | Destabilizing | 0.991 | D | 0.438 | neutral | None | None | None | None | N |
| M/Y | 0.8953 | likely_pathogenic | 0.9006 | pathogenic | -0.76 | Destabilizing | 0.901 | D | 0.501 | 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.