Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1557 | 4894;4895;4896 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| N2AB | 1557 | 4894;4895;4896 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| N2A | 1557 | 4894;4895;4896 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| N2B | 1511 | 4756;4757;4758 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| Novex-1 | 1511 | 4756;4757;4758 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| Novex-2 | 1511 | 4756;4757;4758 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
| Novex-3 | 1557 | 4894;4895;4896 | chr2:178777294;178777293;178777292 | chr2:179642021;179642020;179642019 |
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/I | rs139192633  |
0.324 | None | N | 0.178 | 0.105 | 0.321393169273 | gnomAD-2.1.1 | 3.08727E-04 | None | None | None | None | N | None | 3.04463E-03 | 2.54439E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.78396E-04 |
| M/I | rs139192633 |
0.324 | None | N | 0.178 | 0.105 | 0.321393169273 | gnomAD-3.1.2 | 8.67439E-04 | None | None | None | None | N | None | 2.89533E-03 | 6.5445E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 9.56938E-04 |
| M/I | rs139192633 |
0.324 | None | N | 0.178 | 0.105 | 0.321393169273 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| M/I | rs139192633 |
0.324 | None | N | 0.178 | 0.105 | 0.321393169273 | gnomAD-4.0.0 | 1.86503E-04 | None | None | None | None | N | None | 3.53154E-03 | 3.16667E-04 | None | 0 | 2.23105E-05 | None | 0 | 0 | 0 | 2.19597E-05 | 2.24022E-04 |
| M/T | rs1270728521 |
0.505 | 0.001 | N | 0.271 | 0.121 | 0.559923220125 | gnomAD-4.0.0 | 6.00161E-06 | None | None | None | None | N | None | 1.90042E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.0917 | likely_benign | 0.0866 | benign | -0.814 | Destabilizing | None | N | 0.157 | neutral | None | None | None | None | N |
| M/C | 0.4409 | ambiguous | 0.3986 | ambiguous | -0.585 | Destabilizing | 0.132 | N | 0.373 | neutral | None | None | None | None | N |
| M/D | 0.4208 | ambiguous | 0.3914 | ambiguous | 0.185 | Stabilizing | 0.001 | N | 0.296 | neutral | None | None | None | None | N |
| M/E | 0.1991 | likely_benign | 0.1907 | benign | 0.156 | Stabilizing | None | N | 0.242 | neutral | None | None | None | None | N |
| M/F | 0.1742 | likely_benign | 0.1595 | benign | -0.226 | Destabilizing | 0.009 | N | 0.203 | neutral | None | None | None | None | N |
| M/G | 0.2021 | likely_benign | 0.1954 | benign | -1.037 | Destabilizing | None | N | 0.299 | neutral | None | None | None | None | N |
| M/H | 0.2213 | likely_benign | 0.1935 | benign | -0.111 | Destabilizing | None | N | 0.159 | neutral | None | None | None | None | N |
| M/I | 0.1044 | likely_benign | 0.0941 | benign | -0.299 | Destabilizing | None | N | 0.178 | neutral | N | 0.43905366 | None | None | N |
| M/K | 0.1118 | likely_benign | 0.1029 | benign | 0.151 | Stabilizing | None | N | 0.261 | neutral | N | 0.370514835 | None | None | N |
| M/L | 0.0871 | likely_benign | 0.0837 | benign | -0.299 | Destabilizing | None | N | 0.209 | neutral | N | 0.426945567 | None | None | N |
| M/N | 0.1687 | likely_benign | 0.1552 | benign | 0.305 | Stabilizing | None | N | 0.163 | neutral | None | None | None | None | N |
| M/P | 0.8584 | likely_pathogenic | 0.8543 | pathogenic | -0.442 | Destabilizing | 0.004 | N | 0.301 | neutral | None | None | None | None | N |
| M/Q | 0.1074 | likely_benign | 0.0983 | benign | 0.164 | Stabilizing | None | N | 0.118 | neutral | None | None | None | None | N |
| M/R | 0.1076 | likely_benign | 0.0987 | benign | 0.668 | Stabilizing | None | N | 0.163 | neutral | N | 0.327401717 | None | None | N |
| M/S | 0.1067 | likely_benign | 0.1026 | benign | -0.218 | Destabilizing | None | N | 0.252 | neutral | None | None | None | None | N |
| M/T | 0.071 | likely_benign | 0.0674 | benign | -0.14 | Destabilizing | 0.001 | N | 0.271 | neutral | N | 0.410051893 | None | None | N |
| M/V | 0.0538 | likely_benign | 0.0518 | benign | -0.442 | Destabilizing | None | N | 0.124 | neutral | N | 0.397946261 | None | None | N |
| M/W | 0.5083 | ambiguous | 0.4722 | ambiguous | -0.176 | Destabilizing | 0.316 | N | 0.305 | neutral | None | None | None | None | N |
| M/Y | 0.3504 | ambiguous | 0.3131 | benign | -0.091 | Destabilizing | 0.004 | N | 0.293 | 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.