Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26656 | 80191;80192;80193 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| N2AB | 25015 | 75268;75269;75270 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| N2A | 24088 | 72487;72488;72489 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| N2B | 17591 | 52996;52997;52998 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| Novex-1 | 17716 | 53371;53372;53373 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| Novex-2 | 17783 | 53572;53573;53574 | chr2:178566166;178566165;178566164 | chr2:179430893;179430892;179430891 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs1333413620  |
-0.381 | 0.655 | N | 0.299 | 0.132 | 0.128392430309 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| N/H | rs1333413620 |
-0.381 | 0.655 | N | 0.299 | 0.132 | 0.128392430309 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| N/H | rs1333413620 |
-0.381 | 0.655 | N | 0.299 | 0.132 | 0.128392430309 | gnomAD-4.0.0 | 3.0987E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 7.80982E-05 | 0 | 0 | 0 | 0 |
| N/Y | rs1333413620 |
-0.415 | 0.003 | N | 0.181 | 0.161 | 0.224531998449 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| N/Y | rs1333413620 |
-0.415 | 0.003 | N | 0.181 | 0.161 | 0.224531998449 | gnomAD-4.0.0 | 1.36852E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79907E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1888 | likely_benign | 0.1475 | benign | -0.252 | Destabilizing | 0.129 | N | 0.321 | neutral | None | None | None | None | N |
| N/C | 0.253 | likely_benign | 0.2105 | benign | 0.434 | Stabilizing | 0.983 | D | 0.352 | neutral | None | None | None | None | N |
| N/D | 0.1406 | likely_benign | 0.1261 | benign | 0.062 | Stabilizing | 0.101 | N | 0.211 | neutral | N | 0.38865533 | None | None | N |
| N/E | 0.2914 | likely_benign | 0.2439 | benign | 0.01 | Stabilizing | 0.002 | N | 0.166 | neutral | None | None | None | None | N |
| N/F | 0.3685 | ambiguous | 0.3084 | benign | -0.72 | Destabilizing | 0.002 | N | 0.257 | neutral | None | None | None | None | N |
| N/G | 0.2406 | likely_benign | 0.1968 | benign | -0.395 | Destabilizing | 0.129 | N | 0.205 | neutral | None | None | None | None | N |
| N/H | 0.0876 | likely_benign | 0.0874 | benign | -0.463 | Destabilizing | 0.655 | D | 0.299 | neutral | N | 0.44703163 | None | None | N |
| N/I | 0.2057 | likely_benign | 0.1692 | benign | 0.032 | Stabilizing | 0.351 | N | 0.41 | neutral | N | 0.478623974 | None | None | N |
| N/K | 0.215 | likely_benign | 0.1834 | benign | 0.171 | Stabilizing | 0.213 | N | 0.184 | neutral | N | 0.429829949 | None | None | N |
| N/L | 0.2102 | likely_benign | 0.166 | benign | 0.032 | Stabilizing | 0.264 | N | 0.365 | neutral | None | None | None | None | N |
| N/M | 0.2547 | likely_benign | 0.2165 | benign | 0.41 | Stabilizing | 0.94 | D | 0.333 | neutral | None | None | None | None | N |
| N/P | 0.816 | likely_pathogenic | 0.7334 | pathogenic | -0.037 | Destabilizing | 0.836 | D | 0.378 | neutral | None | None | None | None | N |
| N/Q | 0.2402 | likely_benign | 0.2127 | benign | -0.23 | Destabilizing | 0.264 | N | 0.27 | neutral | None | None | None | None | N |
| N/R | 0.2427 | likely_benign | 0.2016 | benign | 0.255 | Stabilizing | 0.418 | N | 0.264 | neutral | None | None | None | None | N |
| N/S | 0.081 | likely_benign | 0.0687 | benign | 0.02 | Stabilizing | 0.007 | N | 0.135 | neutral | N | 0.373531162 | None | None | N |
| N/T | 0.1182 | likely_benign | 0.0988 | benign | 0.098 | Stabilizing | 0.213 | N | 0.181 | neutral | N | 0.431888819 | None | None | N |
| N/V | 0.2107 | likely_benign | 0.171 | benign | -0.037 | Destabilizing | 0.418 | N | 0.384 | neutral | None | None | None | None | N |
| N/W | 0.592 | likely_pathogenic | 0.5263 | ambiguous | -0.753 | Destabilizing | 0.983 | D | 0.351 | neutral | None | None | None | None | N |
| N/Y | 0.1106 | likely_benign | 0.0993 | benign | -0.467 | Destabilizing | 0.003 | N | 0.181 | neutral | N | 0.414516567 | 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.