Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30218 | 90877;90878;90879 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| N2AB | 28577 | 85954;85955;85956 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| N2A | 27650 | 83173;83174;83175 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| N2B | 21153 | 63682;63683;63684 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| Novex-1 | 21278 | 64057;64058;64059 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| Novex-2 | 21345 | 64258;64259;64260 | chr2:178552248;178552247;178552246 | chr2:179416975;179416974;179416973 |
| 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/A | rs768528782  |
-0.619 | 0.826 | N | 0.505 | 0.118 | 0.289098819767 | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.58901E-04 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs768528782 |
-0.619 | 0.826 | N | 0.505 | 0.118 | 0.289098819767 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85208E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs768528782 |
-0.619 | 0.826 | N | 0.505 | 0.118 | 0.289098819767 | gnomAD-4.0.0 | 6.40741E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.6965E-05 | None | 0 | 0 | 0 | 0 | 2.84544E-05 |
| T/I | rs2154151142 |
None | 0.996 | N | 0.517 | 0.316 | 0.399740851666 | gnomAD-4.0.0 | 6.84353E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65717E-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 | 0.1057 | likely_benign | 0.0998 | benign | -0.921 | Destabilizing | 0.826 | D | 0.505 | neutral | N | 0.506637294 | None | None | N |
| T/C | 0.4147 | ambiguous | 0.4085 | ambiguous | -0.674 | Destabilizing | 0.999 | D | 0.525 | neutral | None | None | None | None | N |
| T/D | 0.3576 | ambiguous | 0.3212 | benign | -0.385 | Destabilizing | 0.884 | D | 0.471 | neutral | None | None | None | None | N |
| T/E | 0.2739 | likely_benign | 0.2626 | benign | -0.311 | Destabilizing | 0.939 | D | 0.477 | neutral | None | None | None | None | N |
| T/F | 0.2707 | likely_benign | 0.2641 | benign | -0.719 | Destabilizing | 0.997 | D | 0.557 | neutral | None | None | None | None | N |
| T/G | 0.3612 | ambiguous | 0.32 | benign | -1.25 | Destabilizing | 0.939 | D | 0.494 | neutral | None | None | None | None | N |
| T/H | 0.2208 | likely_benign | 0.2115 | benign | -1.435 | Destabilizing | 0.991 | D | 0.553 | neutral | None | None | None | None | N |
| T/I | 0.1637 | likely_benign | 0.1563 | benign | -0.111 | Destabilizing | 0.996 | D | 0.517 | neutral | N | 0.506637294 | None | None | N |
| T/K | 0.2296 | likely_benign | 0.2207 | benign | -0.704 | Destabilizing | 0.134 | N | 0.287 | neutral | N | 0.505770503 | None | None | N |
| T/L | 0.1151 | likely_benign | 0.116 | benign | -0.111 | Destabilizing | 0.969 | D | 0.459 | neutral | None | None | None | None | N |
| T/M | 0.1041 | likely_benign | 0.103 | benign | -0.027 | Destabilizing | 0.999 | D | 0.517 | neutral | None | None | None | None | N |
| T/N | 0.1099 | likely_benign | 0.102 | benign | -0.862 | Destabilizing | 0.079 | N | 0.211 | neutral | None | None | None | None | N |
| T/P | 0.4544 | ambiguous | 0.3926 | ambiguous | -0.348 | Destabilizing | 0.996 | D | 0.505 | neutral | N | 0.507330728 | None | None | N |
| T/Q | 0.2213 | likely_benign | 0.2239 | benign | -0.887 | Destabilizing | 0.982 | D | 0.507 | neutral | None | None | None | None | N |
| T/R | 0.204 | likely_benign | 0.2023 | benign | -0.632 | Destabilizing | 0.852 | D | 0.471 | neutral | N | 0.505943861 | None | None | N |
| T/S | 0.1177 | likely_benign | 0.1089 | benign | -1.173 | Destabilizing | 0.826 | D | 0.499 | neutral | N | 0.453861602 | None | None | N |
| T/V | 0.1312 | likely_benign | 0.1293 | benign | -0.348 | Destabilizing | 0.969 | D | 0.462 | neutral | None | None | None | None | N |
| T/W | 0.6325 | likely_pathogenic | 0.6064 | pathogenic | -0.686 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| T/Y | 0.2748 | likely_benign | 0.2547 | benign | -0.423 | Destabilizing | 0.997 | D | 0.559 | 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.