Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14902 | 44929;44930;44931 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| N2AB | 13261 | 40006;40007;40008 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| N2A | 12334 | 37225;37226;37227 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| N2B | 5837 | 17734;17735;17736 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| Novex-1 | 5962 | 18109;18110;18111 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| Novex-2 | 6029 | 18310;18311;18312 | chr2:178624576;178624575;178624574 | chr2:179489303;179489302;179489301 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs1208525940  |
-0.378 | 0.484 | N | 0.523 | 0.322 | 0.325263233342 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/P | rs1208525940 |
-0.378 | 0.484 | N | 0.523 | 0.322 | 0.325263233342 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | rs1208525940 |
-0.378 | 0.484 | N | 0.523 | 0.322 | 0.325263233342 | gnomAD-4.0.0 | 2.56566E-06 | None | None | None | None | N | None | 3.38707E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5845 | likely_pathogenic | 0.6397 | pathogenic | -0.826 | Destabilizing | 0.824 | D | 0.533 | neutral | None | None | None | None | N |
| A/D | 0.3466 | ambiguous | 0.446 | ambiguous | -0.731 | Destabilizing | 0.117 | N | 0.593 | neutral | N | 0.509798611 | None | None | N |
| A/E | 0.2893 | likely_benign | 0.3416 | ambiguous | -0.874 | Destabilizing | 0.149 | N | 0.506 | neutral | None | None | None | None | N |
| A/F | 0.3833 | ambiguous | 0.4716 | ambiguous | -1.003 | Destabilizing | 0.555 | D | 0.631 | neutral | None | None | None | None | N |
| A/G | 0.1904 | likely_benign | 0.2073 | benign | -0.562 | Destabilizing | 0.062 | N | 0.442 | neutral | N | 0.51424657 | None | None | N |
| A/H | 0.5608 | ambiguous | 0.6322 | pathogenic | -0.61 | Destabilizing | 0.935 | D | 0.599 | neutral | None | None | None | None | N |
| A/I | 0.3318 | likely_benign | 0.3811 | ambiguous | -0.428 | Destabilizing | 0.002 | N | 0.38 | neutral | None | None | None | None | N |
| A/K | 0.5213 | ambiguous | 0.6104 | pathogenic | -0.864 | Destabilizing | 0.149 | N | 0.505 | neutral | None | None | None | None | N |
| A/L | 0.262 | likely_benign | 0.3102 | benign | -0.428 | Destabilizing | 0.035 | N | 0.498 | neutral | None | None | None | None | N |
| A/M | 0.3254 | likely_benign | 0.3745 | ambiguous | -0.39 | Destabilizing | 0.555 | D | 0.522 | neutral | None | None | None | None | N |
| A/N | 0.3062 | likely_benign | 0.3708 | ambiguous | -0.524 | Destabilizing | 0.38 | N | 0.597 | neutral | None | None | None | None | N |
| A/P | 0.3532 | ambiguous | 0.4075 | ambiguous | -0.407 | Destabilizing | 0.484 | N | 0.523 | neutral | N | 0.510611983 | None | None | N |
| A/Q | 0.3983 | ambiguous | 0.4393 | ambiguous | -0.818 | Destabilizing | 0.555 | D | 0.537 | neutral | None | None | None | None | N |
| A/R | 0.44 | ambiguous | 0.5292 | ambiguous | -0.353 | Destabilizing | 0.38 | N | 0.539 | neutral | None | None | None | None | N |
| A/S | 0.0972 | likely_benign | 0.0989 | benign | -0.733 | Destabilizing | 0.001 | N | 0.237 | neutral | N | 0.429456133 | None | None | N |
| A/T | 0.0974 | likely_benign | 0.1077 | benign | -0.796 | Destabilizing | None | N | 0.231 | neutral | N | 0.512475641 | None | None | N |
| A/V | 0.1658 | likely_benign | 0.1873 | benign | -0.407 | Destabilizing | 0.002 | N | 0.257 | neutral | N | 0.507546618 | None | None | N |
| A/W | 0.7746 | likely_pathogenic | 0.8429 | pathogenic | -1.155 | Destabilizing | 0.935 | D | 0.659 | neutral | None | None | None | None | N |
| A/Y | 0.567 | likely_pathogenic | 0.6478 | pathogenic | -0.813 | Destabilizing | 0.555 | D | 0.615 | 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.