Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35921 | 107986;107987;107988 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| N2AB | 34280 | 103063;103064;103065 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| N2A | 33353 | 100282;100283;100284 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| N2B | 26856 | 80791;80792;80793 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| Novex-1 | 26981 | 81166;81167;81168 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| Novex-2 | 27048 | 81367;81368;81369 | chr2:178527227;178527226;178527225 | chr2:179391954;179391953;179391952 |
| 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/K | rs749277200  |
None | 0.608 | N | 0.327 | 0.347 | 0.458734620958 | gnomAD-4.0.0 | 6.84226E-07 | None | None | None | -0.446(OBSL1) 0.235(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99463E-07 | 0 | 0 |
| T/M | rs749277200 |
0.148 | 0.998 | D | 0.351 | 0.441 | 0.756686942875 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | 0.374(OBSL1) 0.673(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| T/M | rs749277200 |
0.148 | 0.998 | D | 0.351 | 0.441 | 0.756686942875 | gnomAD-4.0.0 | 6.84226E-06 | None | None | None | 0.374(OBSL1) 0.673(OBSCN) | N | None | 2.98739E-05 | 0 | None | 0 | 0 | None | 1.87308E-05 | 0 | 7.19571E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1366 | likely_benign | 0.1469 | benign | -0.832 | Destabilizing | 0.201 | N | 0.341 | neutral | N | 0.496637384 | None | 0.023(OBSL1) 0.069(OBSCN) | N |
| T/C | 0.6506 | likely_pathogenic | 0.6759 | pathogenic | -0.49 | Destabilizing | 0.992 | D | 0.35 | neutral | None | None | None | -0.234(OBSL1) 0.469(OBSCN) | N |
| T/D | 0.6736 | likely_pathogenic | 0.6715 | pathogenic | -0.118 | Destabilizing | 0.447 | N | 0.345 | neutral | None | None | None | -0.532(OBSL1) 0.12(OBSCN) | N |
| T/E | 0.4961 | ambiguous | 0.4856 | ambiguous | -0.062 | Destabilizing | 0.617 | D | 0.336 | neutral | None | None | None | -0.618(OBSL1) 0.101(OBSCN) | N |
| T/F | 0.4799 | ambiguous | 0.5096 | ambiguous | -0.74 | Destabilizing | 0.92 | D | 0.446 | neutral | None | None | None | -0.365(OBSL1) 0.304(OBSCN) | N |
| T/G | 0.4673 | ambiguous | 0.4877 | ambiguous | -1.143 | Destabilizing | 0.25 | N | 0.398 | neutral | None | None | None | 0.045(OBSL1) 0.035(OBSCN) | N |
| T/H | 0.3846 | ambiguous | 0.3901 | ambiguous | -1.277 | Destabilizing | 0.92 | D | 0.426 | neutral | None | None | None | 0.246(OBSL1) 0.633(OBSCN) | N |
| T/I | 0.36 | ambiguous | 0.3716 | ambiguous | -0.077 | Destabilizing | 0.92 | D | 0.355 | neutral | None | None | None | -0.089(OBSL1) 0.156(OBSCN) | N |
| T/K | 0.3035 | likely_benign | 0.2836 | benign | -0.637 | Destabilizing | 0.608 | D | 0.327 | neutral | N | 0.469450783 | None | -0.446(OBSL1) 0.235(OBSCN) | N |
| T/L | 0.2077 | likely_benign | 0.2216 | benign | -0.077 | Destabilizing | 0.617 | D | 0.336 | neutral | None | None | None | -0.089(OBSL1) 0.156(OBSCN) | N |
| T/M | 0.1534 | likely_benign | 0.1713 | benign | 0.018 | Stabilizing | 0.998 | D | 0.351 | neutral | D | 0.537081284 | None | 0.374(OBSL1) 0.673(OBSCN) | N |
| T/N | 0.2764 | likely_benign | 0.2779 | benign | -0.735 | Destabilizing | 0.021 | N | 0.198 | neutral | None | None | None | -0.316(OBSL1) -0.141(OBSCN) | N |
| T/P | 0.5393 | ambiguous | 0.5013 | ambiguous | -0.295 | Destabilizing | 0.896 | D | 0.361 | neutral | N | 0.507003497 | None | -0.044(OBSL1) 0.131(OBSCN) | N |
| T/Q | 0.3371 | likely_benign | 0.3424 | ambiguous | -0.743 | Destabilizing | 0.85 | D | 0.361 | neutral | None | None | None | -0.311(OBSL1) 0.037(OBSCN) | N |
| T/R | 0.1981 | likely_benign | 0.1886 | benign | -0.513 | Destabilizing | 0.916 | D | 0.357 | neutral | N | 0.474453958 | None | -0.151(OBSL1) 0.208(OBSCN) | N |
| T/S | 0.1541 | likely_benign | 0.1675 | benign | -1.046 | Destabilizing | 0.007 | N | 0.123 | neutral | N | 0.426198651 | None | -0.193(OBSL1) -0.129(OBSCN) | N |
| T/V | 0.2898 | likely_benign | 0.3034 | benign | -0.295 | Destabilizing | 0.617 | D | 0.321 | neutral | None | None | None | -0.044(OBSL1) 0.131(OBSCN) | N |
| T/W | 0.7473 | likely_pathogenic | 0.76 | pathogenic | -0.732 | Destabilizing | 0.992 | D | 0.545 | neutral | None | None | None | -0.639(OBSL1) 0.424(OBSCN) | N |
| T/Y | 0.5285 | ambiguous | 0.5207 | ambiguous | -0.471 | Destabilizing | 0.972 | D | 0.437 | neutral | None | None | None | -0.284(OBSL1) 0.499(OBSCN) | 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.