Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35643 | 107152;107153;107154 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| N2AB | 34002 | 102229;102230;102231 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| N2A | 33075 | 99448;99449;99450 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| N2B | 26578 | 79957;79958;79959 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| Novex-1 | 26703 | 80332;80333;80334 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| Novex-2 | 26770 | 80533;80534;80535 | chr2:178528824;178528823;178528822 | chr2:179393551;179393550;179393549 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1339468653  |
-0.437 | 0.005 | N | 0.225 | 0.083 | None | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40449E-04 |
| V/A | rs1339468653 |
-0.437 | 0.005 | N | 0.225 | 0.083 | None | 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 |
| V/A | rs1339468653 |
-0.437 | 0.005 | N | 0.225 | 0.083 | None | gnomAD-4.0.0 | 1.85898E-06 | None | None | None | None | N | None | 1.33476E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09784E-05 | 1.60097E-05 |
| V/I | rs754459138 |
-0.006 | 0.001 | N | 0.202 | 0.031 | None | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.61302E-04 | None | 0 | None | 0 | 6.24E-05 | 0 |
| V/I | rs754459138 |
-0.006 | 0.001 | N | 0.202 | 0.031 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85208E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| V/I | rs754459138 |
-0.006 | 0.001 | N | 0.202 | 0.031 | None |
Luo (2022)
| None |
HCM 
|
het | None | None | N | Genetic analysis of Hui (CN) HCM family; variant prioritisation in individuals without established pathology; significant echocardiographical differences reported between carrier (n = 4) and non-carrier (n = 12) individuals | None | None | None | None | None | None | None | None | None | None | None |
| V/I | rs754459138 |
-0.006 | 0.001 | N | 0.202 | 0.031 | None | gnomAD-4.0.0 | 9.85272E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.00526E-04 | None | 0 | 0 | 1.25439E-04 | 0 | 3.20184E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.112 | likely_benign | 0.1303 | benign | -0.613 | Destabilizing | 0.005 | N | 0.225 | neutral | N | 0.440319954 | None | None | N |
| V/C | 0.5387 | ambiguous | 0.6375 | pathogenic | -0.782 | Destabilizing | 0.356 | N | 0.289 | neutral | None | None | None | None | N |
| V/D | 0.1935 | likely_benign | 0.2121 | benign | -0.39 | Destabilizing | 0.072 | N | 0.437 | neutral | None | None | None | None | N |
| V/E | 0.1359 | likely_benign | 0.1496 | benign | -0.482 | Destabilizing | 0.012 | N | 0.307 | neutral | N | 0.457692207 | None | None | N |
| V/F | 0.0913 | likely_benign | 0.1072 | benign | -0.683 | Destabilizing | 0.038 | N | 0.361 | neutral | None | None | None | None | N |
| V/G | 0.1826 | likely_benign | 0.2156 | benign | -0.768 | Destabilizing | 0.024 | N | 0.351 | neutral | N | 0.460292582 | None | None | N |
| V/H | 0.2448 | likely_benign | 0.2619 | benign | -0.22 | Destabilizing | 0.214 | N | 0.383 | neutral | None | None | None | None | N |
| V/I | 0.0561 | likely_benign | 0.0588 | benign | -0.344 | Destabilizing | 0.001 | N | 0.202 | neutral | N | 0.460119224 | None | None | N |
| V/K | 0.1021 | likely_benign | 0.1106 | benign | -0.628 | Destabilizing | None | N | 0.168 | neutral | None | None | None | None | N |
| V/L | 0.0981 | likely_benign | 0.1155 | benign | -0.344 | Destabilizing | 0.005 | N | 0.22 | neutral | N | 0.460119224 | None | None | N |
| V/M | 0.0692 | likely_benign | 0.0799 | benign | -0.468 | Destabilizing | 0.001 | N | 0.225 | neutral | None | None | None | None | N |
| V/N | 0.1095 | likely_benign | 0.1205 | benign | -0.457 | Destabilizing | 0.072 | N | 0.436 | neutral | None | None | None | None | N |
| V/P | 0.7142 | likely_pathogenic | 0.8071 | pathogenic | -0.399 | Destabilizing | 0.136 | N | 0.451 | neutral | None | None | None | None | N |
| V/Q | 0.1244 | likely_benign | 0.1321 | benign | -0.669 | Destabilizing | 0.003 | N | 0.243 | neutral | None | None | None | None | N |
| V/R | 0.0795 | likely_benign | 0.09 | benign | -0.079 | Destabilizing | None | N | 0.283 | neutral | None | None | None | None | N |
| V/S | 0.1209 | likely_benign | 0.1319 | benign | -0.835 | Destabilizing | 0.016 | N | 0.304 | neutral | None | None | None | None | N |
| V/T | 0.0852 | likely_benign | 0.0952 | benign | -0.823 | Destabilizing | None | N | 0.187 | neutral | None | None | None | None | N |
| V/W | 0.4625 | ambiguous | 0.5518 | ambiguous | -0.768 | Destabilizing | 0.676 | D | 0.361 | neutral | None | None | None | None | N |
| V/Y | 0.2922 | likely_benign | 0.3266 | benign | -0.491 | Destabilizing | None | N | 0.267 | 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.