Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30573 | 91942;91943;91944 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| N2AB | 28932 | 87019;87020;87021 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| N2A | 28005 | 84238;84239;84240 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| N2B | 21508 | 64747;64748;64749 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| Novex-1 | 21633 | 65122;65123;65124 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| Novex-2 | 21700 | 65323;65324;65325 | chr2:178550121;178550120;178550119 | chr2:179414848;179414847;179414846 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs756674702  |
-1.515 | None | N | 0.083 | 0.082 | 0.364141725642 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| M/I | rs756674702 |
-1.515 | None | N | 0.083 | 0.082 | 0.364141725642 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85838E-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 | 0.2361 | likely_benign | 0.2739 | benign | -2.907 | Highly Destabilizing | 0.006 | N | 0.29 | neutral | None | None | None | None | N |
| M/C | 0.5089 | ambiguous | 0.4971 | ambiguous | -1.964 | Destabilizing | 0.781 | D | 0.495 | neutral | None | None | None | None | N |
| M/D | 0.7828 | likely_pathogenic | 0.8289 | pathogenic | -1.889 | Destabilizing | 0.251 | N | 0.535 | neutral | None | None | None | None | N |
| M/E | 0.4577 | ambiguous | 0.5067 | ambiguous | -1.782 | Destabilizing | 0.251 | N | 0.454 | neutral | None | None | None | None | N |
| M/F | 0.2496 | likely_benign | 0.2895 | benign | -1.485 | Destabilizing | 0.064 | N | 0.369 | neutral | None | None | None | None | N |
| M/G | 0.5115 | ambiguous | 0.5736 | pathogenic | -3.297 | Highly Destabilizing | 0.121 | N | 0.433 | neutral | None | None | None | None | N |
| M/H | 0.4953 | ambiguous | 0.5236 | ambiguous | -2.43 | Highly Destabilizing | 0.781 | D | 0.516 | neutral | None | None | None | None | N |
| M/I | 0.1344 | likely_benign | 0.1686 | benign | -1.813 | Destabilizing | None | N | 0.083 | neutral | N | 0.397702541 | None | None | N |
| M/K | 0.2572 | likely_benign | 0.2758 | benign | -1.752 | Destabilizing | 0.094 | N | 0.436 | neutral | N | 0.51433771 | None | None | N |
| M/L | 0.1089 | likely_benign | 0.1095 | benign | -1.813 | Destabilizing | 0.001 | N | 0.135 | neutral | N | 0.441608034 | None | None | N |
| M/N | 0.4814 | ambiguous | 0.5384 | ambiguous | -1.678 | Destabilizing | 0.505 | D | 0.531 | neutral | None | None | None | None | N |
| M/P | 0.9044 | likely_pathogenic | 0.9413 | pathogenic | -2.159 | Highly Destabilizing | 0.505 | D | 0.525 | neutral | None | None | None | None | N |
| M/Q | 0.3025 | likely_benign | 0.3154 | benign | -1.654 | Destabilizing | 0.505 | D | 0.458 | neutral | None | None | None | None | N |
| M/R | 0.2559 | likely_benign | 0.2742 | benign | -1.301 | Destabilizing | 0.202 | N | 0.525 | neutral | N | 0.50527551 | None | None | N |
| M/S | 0.3116 | likely_benign | 0.3514 | ambiguous | -2.304 | Highly Destabilizing | 0.064 | N | 0.4 | neutral | None | None | None | None | N |
| M/T | 0.1031 | likely_benign | 0.1152 | benign | -2.092 | Highly Destabilizing | 0.049 | N | 0.334 | neutral | N | 0.47529932 | None | None | N |
| M/V | 0.0581 | likely_benign | 0.0632 | benign | -2.159 | Highly Destabilizing | None | N | 0.083 | neutral | N | 0.432564476 | None | None | N |
| M/W | 0.5336 | ambiguous | 0.5748 | pathogenic | -1.488 | Destabilizing | 0.931 | D | 0.475 | neutral | None | None | None | None | N |
| M/Y | 0.4706 | ambiguous | 0.5016 | ambiguous | -1.66 | Destabilizing | 0.251 | N | 0.485 | 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.