Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21392 | 64399;64400;64401 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| N2AB | 19751 | 59476;59477;59478 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| N2A | 18824 | 56695;56696;56697 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| N2B | 12327 | 37204;37205;37206 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| Novex-1 | 12452 | 37579;37580;37581 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| Novex-2 | 12519 | 37780;37781;37782 | chr2:178586727;178586726;178586725 | chr2:179451454;179451453;179451452 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs72646859  |
-0.102 | 1.0 | N | 0.745 | 0.302 | None | gnomAD-2.1.1 | 6.1088E-04 | None | None | None | None | I | None | 1.65399E-04 | 1.98154E-04 | None | 0 | 1.70068E-03 | None | 6.54E-05 | None | 0 | 9.69219E-04 | 1.40449E-04 |
| R/C | rs72646859 |
-0.102 | 1.0 | N | 0.745 | 0.302 | None | gnomAD-3.1.2 | 5.39296E-04 | None | None | None | None | I | None | 1.44802E-04 | 4.58776E-04 | 0 | 0 | 9.70874E-04 | None | 0 | 3.16456E-03 | 9.26634E-04 | 0 | 0 |
| R/C | rs72646859 |
-0.102 | 1.0 | N | 0.745 | 0.302 | None | gnomAD-4.0.0 | 8.00317E-04 | None | None | None | None | I | None | 1.20029E-04 | 2.66764E-04 | None | 0 | 1.20643E-03 | None | 0 | 3.30688E-04 | 9.72561E-04 | 6.59036E-05 | 9.12876E-04 |
| R/G | None | None | 1.0 | N | 0.536 | 0.266 | 0.455996456696 | gnomAD-4.0.0 | 6.84489E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65755E-05 |
| R/H | None | -0.873 | 1.0 | N | 0.739 | 0.362 | None | gnomAD-2.1.1 | 6.43E-05 | None | None | None | None | I | None | 4.14E-05 | 1.98154E-04 | None | 0 | 0 | None | 0 | None | 4E-05 | 7.03E-05 | 0 |
| R/H | None | -0.873 | 1.0 | N | 0.739 | 0.362 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | I | None | 4.83E-05 | 1.31027E-04 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 0 |
| R/H | None | -0.873 | 1.0 | N | 0.739 | 0.362 | None | gnomAD-4.0.0 | 5.1457E-05 | None | None | None | None | I | None | 5.34331E-05 | 1.66767E-04 | None | 3.38066E-05 | 0 | None | 6.24902E-05 | 0 | 4.91795E-05 | 2.1965E-05 | 6.40841E-05 |
| R/L | rs777176324 |
0.27 | 1.0 | N | 0.536 | 0.407 | 0.499985177359 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| R/L | rs777176324 |
0.27 | 1.0 | N | 0.536 | 0.407 | 0.499985177359 | gnomAD-4.0.0 | 1.36899E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87273E-05 | 0 | 8.99789E-07 | 0 | 0 |
| R/P | rs777176324 |
None | 1.0 | N | 0.667 | 0.378 | 0.388653054685 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/P | rs777176324 |
None | 1.0 | N | 0.667 | 0.378 | 0.388653054685 | gnomAD-4.0.0 | 6.57626E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47102E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.953 | likely_pathogenic | 0.9065 | pathogenic | -0.328 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | I |
| R/C | 0.7518 | likely_pathogenic | 0.6017 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.517804011 | None | None | I |
| R/D | 0.9705 | likely_pathogenic | 0.9514 | pathogenic | -0.091 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| R/E | 0.8965 | likely_pathogenic | 0.8396 | pathogenic | -0.023 | Destabilizing | 0.999 | D | 0.608 | neutral | None | None | None | None | I |
| R/F | 0.9386 | likely_pathogenic | 0.894 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| R/G | 0.8854 | likely_pathogenic | 0.7947 | pathogenic | -0.549 | Destabilizing | 1.0 | D | 0.536 | neutral | N | 0.500853046 | None | None | I |
| R/H | 0.3694 | ambiguous | 0.2447 | benign | -1.017 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.450944301 | None | None | I |
| R/I | 0.918 | likely_pathogenic | 0.8442 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| R/K | 0.4758 | ambiguous | 0.3439 | ambiguous | -0.355 | Destabilizing | 0.998 | D | 0.464 | neutral | None | None | None | None | I |
| R/L | 0.8467 | likely_pathogenic | 0.759 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.536 | neutral | N | 0.512203403 | None | None | I |
| R/M | 0.9069 | likely_pathogenic | 0.8111 | pathogenic | -0.03 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| R/N | 0.9442 | likely_pathogenic | 0.8982 | pathogenic | 0.083 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| R/P | 0.9874 | likely_pathogenic | 0.9795 | pathogenic | 0.065 | Stabilizing | 1.0 | D | 0.667 | neutral | N | 0.498698175 | None | None | I |
| R/Q | 0.4722 | ambiguous | 0.3274 | benign | -0.121 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| R/S | 0.9521 | likely_pathogenic | 0.9092 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.6 | neutral | N | 0.458792993 | None | None | I |
| R/T | 0.9131 | likely_pathogenic | 0.8207 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.594 | neutral | None | None | None | None | I |
| R/V | 0.9317 | likely_pathogenic | 0.8772 | pathogenic | 0.065 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| R/W | 0.5183 | ambiguous | 0.3958 | ambiguous | -0.422 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/Y | 0.8299 | likely_pathogenic | 0.7317 | pathogenic | -0.043 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | I |
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.