Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23970 | 72133;72134;72135 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| N2AB | 22329 | 67210;67211;67212 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| N2A | 21402 | 64429;64430;64431 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| N2B | 14905 | 44938;44939;44940 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| Novex-1 | 15030 | 45313;45314;45315 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| Novex-2 | 15097 | 45514;45515;45516 | chr2:178574224;178574223;178574222 | chr2:179438951;179438950;179438949 |
| 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/Q | rs727503563  |
-0.074 | 1.0 | N | 0.668 | 0.376 | 0.284150004643 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| R/Q | rs727503563 |
-0.074 | 1.0 | N | 0.668 | 0.376 | 0.284150004643 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs727503563 |
-0.074 | 1.0 | N | 0.668 | 0.376 | 0.284150004643 | gnomAD-4.0.0 | 7.43857E-06 | None | None | None | None | N | None | 2.6708E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78221E-06 | 2.19621E-05 | 0 |
| R/W | rs748041610 |
-0.385 | 1.0 | N | 0.777 | 0.529 | 0.367042808489 | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.55167E-04 | None | 1.30762E-04 | None | 0 | 7.85E-06 | 0 |
| R/W | rs748041610 |
-0.385 | 1.0 | N | 0.777 | 0.529 | 0.367042808489 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93648E-04 | None | 0 | 0 | 1.47E-05 | 4.14079E-04 | 0 |
| R/W | rs748041610 |
-0.385 | 1.0 | N | 0.777 | 0.529 | 0.367042808489 | gnomAD-4.0.0 | 2.10762E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.70601E-05 | None | 0 | 0 | 1.10214E-05 | 1.64701E-04 | 4.80492E-05 |
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 | 0.8813 | likely_pathogenic | 0.9038 | pathogenic | 0.043 | Stabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| R/C | 0.494 | ambiguous | 0.567 | pathogenic | -0.334 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| R/D | 0.9427 | likely_pathogenic | 0.9504 | pathogenic | -0.269 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/E | 0.8137 | likely_pathogenic | 0.8302 | pathogenic | -0.216 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | N |
| R/F | 0.8861 | likely_pathogenic | 0.9062 | pathogenic | -0.272 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/G | 0.7705 | likely_pathogenic | 0.8193 | pathogenic | -0.108 | Destabilizing | 1.0 | D | 0.581 | neutral | N | 0.507261731 | None | None | N |
| R/H | 0.2559 | likely_benign | 0.2831 | benign | -0.596 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/I | 0.7014 | likely_pathogenic | 0.7225 | pathogenic | 0.396 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/K | 0.2567 | likely_benign | 0.2651 | benign | -0.181 | Destabilizing | 0.998 | D | 0.591 | neutral | None | None | None | None | N |
| R/L | 0.6626 | likely_pathogenic | 0.6951 | pathogenic | 0.396 | Stabilizing | 1.0 | D | 0.581 | neutral | N | 0.466329128 | None | None | N |
| R/M | 0.7667 | likely_pathogenic | 0.7879 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/N | 0.9007 | likely_pathogenic | 0.916 | pathogenic | -0.162 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/P | 0.8748 | likely_pathogenic | 0.9064 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.482307016 | None | None | N |
| R/Q | 0.2584 | likely_benign | 0.2952 | benign | -0.172 | Destabilizing | 1.0 | D | 0.668 | neutral | N | 0.517921441 | None | None | N |
| R/S | 0.9096 | likely_pathogenic | 0.9305 | pathogenic | -0.354 | Destabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | N |
| R/T | 0.8024 | likely_pathogenic | 0.8259 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| R/V | 0.7945 | likely_pathogenic | 0.8236 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/W | 0.4775 | ambiguous | 0.5403 | ambiguous | -0.452 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.511046788 | None | None | N |
| R/Y | 0.7327 | likely_pathogenic | 0.7709 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.706 | prob.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.