Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19631 | 59116;59117;59118 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| N2AB | 17990 | 54193;54194;54195 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| N2A | 17063 | 51412;51413;51414 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| N2B | 10566 | 31921;31922;31923 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| Novex-1 | 10691 | 32296;32297;32298 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| Novex-2 | 10758 | 32497;32498;32499 | chr2:178593317;178593316;178593315 | chr2:179458044;179458043;179458042 |
| 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/H | None | None | 0.484 | N | 0.397 | 0.208 | 0.198526703765 | gnomAD-4.0.0 | 1.36872E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79924E-06 | 0 | 0 |
| D/Y | rs565837633  |
-0.27 | 0.741 | N | 0.421 | 0.242 | 0.54456359225 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.67485E-04 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs565837633 |
-0.27 | 0.741 | N | 0.421 | 0.242 | 0.54456359225 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.88802E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs565837633 |
-0.27 | 0.741 | N | 0.421 | 0.242 | 0.54456359225 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| D/Y | rs565837633 |
-0.27 | 0.741 | N | 0.421 | 0.242 | 0.54456359225 | gnomAD-4.0.0 | 4.33893E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.5639E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1461 | likely_benign | 0.1217 | benign | 0.042 | Stabilizing | 0.027 | N | 0.327 | neutral | N | 0.489678834 | None | None | I |
| D/C | 0.6069 | likely_pathogenic | 0.5258 | ambiguous | -0.119 | Destabilizing | 0.935 | D | 0.443 | neutral | None | None | None | None | I |
| D/E | 0.0768 | likely_benign | 0.0665 | benign | -0.231 | Destabilizing | None | N | 0.092 | neutral | N | 0.422800481 | None | None | I |
| D/F | 0.4973 | ambiguous | 0.4246 | ambiguous | 0.03 | Stabilizing | 0.791 | D | 0.407 | neutral | None | None | None | None | I |
| D/G | 0.1833 | likely_benign | 0.1491 | benign | -0.09 | Destabilizing | 0.117 | N | 0.362 | neutral | N | 0.478000403 | None | None | I |
| D/H | 0.2962 | likely_benign | 0.2385 | benign | 0.582 | Stabilizing | 0.484 | N | 0.397 | neutral | N | 0.485870525 | None | None | I |
| D/I | 0.2379 | likely_benign | 0.1905 | benign | 0.323 | Stabilizing | 0.555 | D | 0.439 | neutral | None | None | None | None | I |
| D/K | 0.2727 | likely_benign | 0.1991 | benign | 0.475 | Stabilizing | 0.035 | N | 0.353 | neutral | None | None | None | None | I |
| D/L | 0.2641 | likely_benign | 0.2126 | benign | 0.323 | Stabilizing | 0.149 | N | 0.392 | neutral | None | None | None | None | I |
| D/M | 0.4067 | ambiguous | 0.3341 | benign | 0.112 | Stabilizing | 0.935 | D | 0.393 | neutral | None | None | None | None | I |
| D/N | 0.113 | likely_benign | 0.0986 | benign | 0.159 | Stabilizing | 0.117 | N | 0.323 | neutral | N | 0.480675349 | None | None | I |
| D/P | 0.7793 | likely_pathogenic | 0.699 | pathogenic | 0.249 | Stabilizing | 0.262 | N | 0.418 | neutral | None | None | None | None | I |
| D/Q | 0.213 | likely_benign | 0.1751 | benign | 0.188 | Stabilizing | 0.007 | N | 0.123 | neutral | None | None | None | None | I |
| D/R | 0.3755 | ambiguous | 0.2997 | benign | 0.703 | Stabilizing | 0.081 | N | 0.395 | neutral | None | None | None | None | I |
| D/S | 0.1345 | likely_benign | 0.1107 | benign | 0.083 | Stabilizing | 0.035 | N | 0.305 | neutral | None | None | None | None | I |
| D/T | 0.1752 | likely_benign | 0.1401 | benign | 0.196 | Stabilizing | 0.149 | N | 0.363 | neutral | None | None | None | None | I |
| D/V | 0.1508 | likely_benign | 0.1186 | benign | 0.249 | Stabilizing | 0.117 | N | 0.393 | neutral | N | 0.43894337 | None | None | I |
| D/W | 0.821 | likely_pathogenic | 0.7823 | pathogenic | 0.087 | Stabilizing | 0.935 | D | 0.545 | neutral | None | None | None | None | I |
| D/Y | 0.1936 | likely_benign | 0.17 | benign | 0.259 | Stabilizing | 0.741 | D | 0.421 | neutral | N | 0.506688514 | None | None | I |
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.