Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24076 | 72451;72452;72453 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| N2AB | 22435 | 67528;67529;67530 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| N2A | 21508 | 64747;64748;64749 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| N2B | 15011 | 45256;45257;45258 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| Novex-1 | 15136 | 45631;45632;45633 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| Novex-2 | 15203 | 45832;45833;45834 | chr2:178573906;178573905;178573904 | chr2:179438633;179438632;179438631 |
| 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/V | rs202098308  |
-1.677 | 0.64 | N | 0.596 | 0.114 | None | gnomAD-2.1.1 | 7.17E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 2.00497E-04 | 1.17531E-04 | 0 |
| L/V | rs202098308 |
-1.677 | 0.64 | N | 0.596 | 0.114 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47085E-04 | 0 | 0 |
| L/V | rs202098308 |
-1.677 | 0.64 | N | 0.596 | 0.114 | None | gnomAD-4.0.0 | 4.90226E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.876E-04 | 0 | 5.51612E-05 | 0 | 3.20698E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2812 | likely_benign | 0.28 | benign | -2.528 | Highly Destabilizing | 0.851 | D | 0.621 | neutral | None | None | None | None | N |
| L/C | 0.4897 | ambiguous | 0.4996 | ambiguous | -1.81 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| L/D | 0.8131 | likely_pathogenic | 0.8095 | pathogenic | -2.433 | Highly Destabilizing | 0.976 | D | 0.777 | deleterious | None | None | None | None | N |
| L/E | 0.4662 | ambiguous | 0.4572 | ambiguous | -2.297 | Highly Destabilizing | 0.976 | D | 0.746 | deleterious | None | None | None | None | N |
| L/F | 0.1683 | likely_benign | 0.1949 | benign | -1.629 | Destabilizing | 0.938 | D | 0.623 | neutral | N | 0.480494496 | None | None | N |
| L/G | 0.6193 | likely_pathogenic | 0.6055 | pathogenic | -3.011 | Highly Destabilizing | 0.952 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/H | 0.323 | likely_benign | 0.3453 | ambiguous | -2.317 | Highly Destabilizing | 0.993 | D | 0.763 | deleterious | None | None | None | None | N |
| L/I | 0.0878 | likely_benign | 0.0854 | benign | -1.177 | Destabilizing | 0.211 | N | 0.361 | neutral | N | 0.433183338 | None | None | N |
| L/K | 0.3701 | ambiguous | 0.3569 | ambiguous | -1.963 | Destabilizing | 0.976 | D | 0.707 | prob.neutral | None | None | None | None | N |
| L/M | 0.0917 | likely_benign | 0.0935 | benign | -0.987 | Destabilizing | 0.507 | D | 0.36 | neutral | None | None | None | None | N |
| L/N | 0.4706 | ambiguous | 0.4543 | ambiguous | -2.032 | Highly Destabilizing | 0.976 | D | 0.777 | deleterious | None | None | None | None | N |
| L/P | 0.9102 | likely_pathogenic | 0.8947 | pathogenic | -1.603 | Destabilizing | 0.988 | D | 0.791 | deleterious | None | None | None | None | N |
| L/Q | 0.2096 | likely_benign | 0.209 | benign | -2.044 | Highly Destabilizing | 0.988 | D | 0.748 | deleterious | None | None | None | None | N |
| L/R | 0.2809 | likely_benign | 0.2785 | benign | -1.47 | Destabilizing | 0.976 | D | 0.745 | deleterious | None | None | None | None | N |
| L/S | 0.3835 | ambiguous | 0.3966 | ambiguous | -2.758 | Highly Destabilizing | 0.211 | N | 0.496 | neutral | D | 0.532232825 | None | None | N |
| L/T | 0.177 | likely_benign | 0.1714 | benign | -2.485 | Highly Destabilizing | 0.851 | D | 0.656 | neutral | None | None | None | None | N |
| L/V | 0.0934 | likely_benign | 0.0937 | benign | -1.603 | Destabilizing | 0.64 | D | 0.596 | neutral | N | 0.465621044 | None | None | N |
| L/W | 0.2991 | likely_benign | 0.3332 | benign | -1.888 | Destabilizing | 0.997 | D | 0.725 | prob.delet. | None | None | None | None | N |
| L/Y | 0.358 | ambiguous | 0.3931 | ambiguous | -1.662 | Destabilizing | 0.076 | N | 0.502 | 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.