Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17953 | 54082;54083;54084 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| N2AB | 16312 | 49159;49160;49161 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| N2A | 15385 | 46378;46379;46380 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| N2B | 8888 | 26887;26888;26889 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| Novex-1 | 9013 | 27262;27263;27264 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| Novex-2 | 9080 | 27463;27464;27465 | chr2:178605438;178605437;178605436 | chr2:179470165;179470164;179470163 |
| 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/D | None | None | 0.006 | N | 0.241 | 0.187 | 0.171388866994 | gnomAD-4.0.0 | 6.87557E-07 | None | None | None | None | N | None | 0 | 2.25734E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | rs769210939  |
-0.233 | 0.651 | N | 0.417 | 0.08 | 0.0954503805726 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.95212E-04 | None | 0 | None | 0 | 0 | 0 |
| N/K | rs769210939 |
-0.233 | 0.651 | N | 0.417 | 0.08 | 0.0954503805726 | gnomAD-4.0.0 | 4.12561E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.52122E-04 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs2054557053 |
None | 0.278 | N | 0.443 | 0.144 | 0.168933306366 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| N/Y | None | None | 0.976 | N | 0.562 | 0.323 | 0.447410926215 | gnomAD-4.0.0 | 6.87557E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.02915E-07 | 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 | 0.5253 | ambiguous | 0.4806 | ambiguous | -0.571 | Destabilizing | 0.505 | D | 0.471 | neutral | None | None | None | None | N |
| N/C | 0.5579 | ambiguous | 0.5352 | ambiguous | 0.21 | Stabilizing | 0.995 | D | 0.617 | neutral | None | None | None | None | N |
| N/D | 0.5188 | ambiguous | 0.4454 | ambiguous | -0.11 | Destabilizing | 0.006 | N | 0.241 | neutral | N | 0.402729066 | None | None | N |
| N/E | 0.838 | likely_pathogenic | 0.781 | pathogenic | -0.045 | Destabilizing | 0.553 | D | 0.469 | neutral | None | None | None | None | N |
| N/F | 0.837 | likely_pathogenic | 0.8039 | pathogenic | -0.447 | Destabilizing | 0.982 | D | 0.604 | neutral | None | None | None | None | N |
| N/G | 0.5973 | likely_pathogenic | 0.5616 | ambiguous | -0.878 | Destabilizing | 0.505 | D | 0.457 | neutral | None | None | None | None | N |
| N/H | 0.2915 | likely_benign | 0.2521 | benign | -0.742 | Destabilizing | 0.976 | D | 0.476 | neutral | N | 0.480573775 | None | None | N |
| N/I | 0.6169 | likely_pathogenic | 0.5471 | ambiguous | 0.188 | Stabilizing | 0.868 | D | 0.623 | neutral | N | 0.498292744 | None | None | N |
| N/K | 0.8574 | likely_pathogenic | 0.8004 | pathogenic | -0.211 | Destabilizing | 0.651 | D | 0.417 | neutral | N | 0.450770943 | None | None | N |
| N/L | 0.4881 | ambiguous | 0.4507 | ambiguous | 0.188 | Stabilizing | 0.712 | D | 0.547 | neutral | None | None | None | None | N |
| N/M | 0.603 | likely_pathogenic | 0.5596 | ambiguous | 0.449 | Stabilizing | 0.995 | D | 0.555 | neutral | None | None | None | None | N |
| N/P | 0.7047 | likely_pathogenic | 0.6435 | pathogenic | -0.035 | Destabilizing | 0.946 | D | 0.568 | neutral | None | None | None | None | N |
| N/Q | 0.7176 | likely_pathogenic | 0.6719 | pathogenic | -0.595 | Destabilizing | 0.946 | D | 0.512 | neutral | None | None | None | None | N |
| N/R | 0.8195 | likely_pathogenic | 0.7693 | pathogenic | -0.295 | Destabilizing | 0.946 | D | 0.481 | neutral | None | None | None | None | N |
| N/S | 0.1541 | likely_benign | 0.1412 | benign | -0.616 | Destabilizing | 0.278 | N | 0.443 | neutral | N | 0.397475175 | None | None | N |
| N/T | 0.2784 | likely_benign | 0.2367 | benign | -0.372 | Destabilizing | 0.003 | N | 0.209 | neutral | N | 0.372539445 | None | None | N |
| N/V | 0.5584 | ambiguous | 0.5067 | ambiguous | -0.035 | Destabilizing | 0.712 | D | 0.553 | neutral | None | None | None | None | N |
| N/W | 0.9101 | likely_pathogenic | 0.8908 | pathogenic | -0.323 | Destabilizing | 0.995 | D | 0.662 | prob.neutral | None | None | None | None | N |
| N/Y | 0.4618 | ambiguous | 0.3887 | ambiguous | -0.103 | Destabilizing | 0.976 | D | 0.562 | neutral | N | 0.4800537 | 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.