Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18642 | 56149;56150;56151 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| N2AB | 17001 | 51226;51227;51228 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| N2A | 16074 | 48445;48446;48447 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| N2B | 9577 | 28954;28955;28956 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| Novex-1 | 9702 | 29329;29330;29331 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| Novex-2 | 9769 | 29530;29531;29532 | chr2:178600980;178600979;178600978 | chr2:179465707;179465706;179465705 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/Q | rs140714512  |
-1.503 | 0.879 | N | 0.644 | 0.247 | None | gnomAD-2.1.1 | 4.83133E-04 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 5.3367E-03 | 0 | None | 6.54E-05 | None | 0 | 5.41822E-04 | 9.83699E-04 |
| L/Q | rs140714512 |
-1.503 | 0.879 | N | 0.644 | 0.247 | None | gnomAD-3.1.2 | 4.67228E-04 | None | None | None | None | N | None | 2.41E-05 | 5.24728E-04 | 0 | 6.62442E-03 | 0 | None | 0 | 3.16456E-03 | 5.59268E-04 | 0 | 0 |
| L/Q | rs140714512 |
-1.503 | 0.879 | N | 0.644 | 0.247 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| L/Q | rs140714512 |
-1.503 | 0.879 | N | 0.644 | 0.247 | None | gnomAD-4.0.0 | 3.50269E-04 | None | None | None | None | N | None | 1.33394E-05 | 1.66761E-04 | None | 5.57885E-03 | 0 | None | 1.56235E-05 | 9.91736E-04 | 2.80667E-04 | 3.29518E-05 | 7.6859E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3064 | likely_benign | 0.2443 | benign | -1.721 | Destabilizing | 0.218 | N | 0.465 | neutral | None | None | None | None | N |
| L/C | 0.4026 | ambiguous | 0.3677 | ambiguous | -0.934 | Destabilizing | 0.973 | D | 0.605 | neutral | None | None | None | None | N |
| L/D | 0.6747 | likely_pathogenic | 0.6364 | pathogenic | -1.653 | Destabilizing | 0.826 | D | 0.68 | prob.neutral | None | None | None | None | N |
| L/E | 0.3775 | ambiguous | 0.3368 | benign | -1.508 | Destabilizing | 0.826 | D | 0.644 | neutral | None | None | None | None | N |
| L/F | 0.3422 | ambiguous | 0.3098 | benign | -1.015 | Destabilizing | 0.906 | D | 0.528 | neutral | None | None | None | None | N |
| L/G | 0.4667 | ambiguous | 0.3991 | ambiguous | -2.156 | Highly Destabilizing | 0.826 | D | 0.625 | neutral | None | None | None | None | N |
| L/H | 0.3973 | ambiguous | 0.3475 | ambiguous | -1.43 | Destabilizing | 0.991 | D | 0.724 | prob.delet. | None | None | None | None | N |
| L/I | 0.2263 | likely_benign | 0.1956 | benign | -0.529 | Destabilizing | 0.404 | N | 0.45 | neutral | None | None | None | None | N |
| L/K | 0.2603 | likely_benign | 0.2423 | benign | -1.209 | Destabilizing | 0.826 | D | 0.577 | neutral | None | None | None | None | N |
| L/M | 0.1214 | likely_benign | 0.1134 | benign | -0.429 | Destabilizing | 0.879 | D | 0.569 | neutral | N | 0.502933346 | None | None | N |
| L/N | 0.2523 | likely_benign | 0.2317 | benign | -1.396 | Destabilizing | 0.826 | D | 0.671 | neutral | None | None | None | None | N |
| L/P | 0.2157 | likely_benign | 0.1824 | benign | -0.901 | Destabilizing | 0.879 | D | 0.689 | prob.neutral | N | 0.473573231 | None | None | N |
| L/Q | 0.1979 | likely_benign | 0.1716 | benign | -1.374 | Destabilizing | 0.879 | D | 0.644 | neutral | N | 0.505453576 | None | None | N |
| L/R | 0.2488 | likely_benign | 0.2215 | benign | -0.833 | Destabilizing | 0.782 | D | 0.629 | neutral | N | 0.468935416 | None | None | N |
| L/S | 0.3364 | likely_benign | 0.2651 | benign | -2.014 | Highly Destabilizing | 0.404 | N | 0.505 | neutral | None | None | None | None | N |
| L/T | 0.1165 | likely_benign | 0.0914 | benign | -1.737 | Destabilizing | 0.002 | N | 0.319 | neutral | None | None | None | None | N |
| L/V | 0.1819 | likely_benign | 0.1532 | benign | -0.901 | Destabilizing | 0.174 | N | 0.494 | neutral | N | 0.507896449 | None | None | N |
| L/W | 0.4758 | ambiguous | 0.4461 | ambiguous | -1.304 | Destabilizing | 0.991 | D | 0.692 | prob.neutral | None | None | None | None | N |
| L/Y | 0.5222 | ambiguous | 0.4683 | ambiguous | -0.954 | Destabilizing | 0.906 | D | 0.596 | 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.