Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18266 | 55021;55022;55023 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| N2AB | 16625 | 50098;50099;50100 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| N2A | 15698 | 47317;47318;47319 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| N2B | 9201 | 27826;27827;27828 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| Novex-1 | 9326 | 28201;28202;28203 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| Novex-2 | 9393 | 28402;28403;28404 | chr2:178603891;178603890;178603889 | chr2:179468618;179468617;179468616 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs199837769  |
-2.147 | 0.999 | N | 0.598 | 0.353 | None | gnomAD-2.1.1 | 1.15539E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.52235E-04 | 0 |
| A/S | rs199837769 |
-2.147 | 0.999 | N | 0.598 | 0.353 | None | gnomAD-3.1.2 | 1.1844E-04 | None | None | None | None | N | None | 0 | 1.31199E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.35509E-04 | 0 | 0 |
| A/S | rs199837769 |
-2.147 | 0.999 | N | 0.598 | 0.353 | None | gnomAD-4.0.0 | 1.40839E-04 | None | None | None | None | N | None | 0 | 3.35762E-05 | None | 0 | 0 | None | 0 | 0 | 1.86611E-04 | 0 | 8.10504E-05 |
| A/T | None | None | 1.0 | N | 0.753 | 0.271 | 0.340510301474 | gnomAD-4.0.0 | 1.38351E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81774E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5999 | likely_pathogenic | 0.5701 | pathogenic | -1.826 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| A/D | 0.9864 | likely_pathogenic | 0.9853 | pathogenic | -2.76 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| A/E | 0.9688 | likely_pathogenic | 0.9669 | pathogenic | -2.654 | Highly Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.511372275 | None | None | N |
| A/F | 0.9211 | likely_pathogenic | 0.9039 | pathogenic | -1.039 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/G | 0.5212 | ambiguous | 0.4804 | ambiguous | -1.63 | Destabilizing | 0.999 | D | 0.564 | neutral | N | 0.485381208 | None | None | N |
| A/H | 0.9823 | likely_pathogenic | 0.9806 | pathogenic | -1.665 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| A/I | 0.7051 | likely_pathogenic | 0.6138 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/K | 0.9893 | likely_pathogenic | 0.9891 | pathogenic | -1.408 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| A/L | 0.6064 | likely_pathogenic | 0.5892 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| A/M | 0.7467 | likely_pathogenic | 0.6962 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| A/N | 0.9671 | likely_pathogenic | 0.9618 | pathogenic | -1.643 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| A/P | 0.6929 | likely_pathogenic | 0.6267 | pathogenic | -0.642 | Destabilizing | 1.0 | D | 0.818 | deleterious | N | 0.479883799 | None | None | N |
| A/Q | 0.9519 | likely_pathogenic | 0.9487 | pathogenic | -1.669 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/R | 0.9635 | likely_pathogenic | 0.9644 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| A/S | 0.3271 | likely_benign | 0.3038 | benign | -1.987 | Destabilizing | 0.999 | D | 0.598 | neutral | N | 0.47507486 | None | None | N |
| A/T | 0.542 | ambiguous | 0.4461 | ambiguous | -1.781 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.499468967 | None | None | N |
| A/V | 0.4561 | ambiguous | 0.373 | ambiguous | -0.642 | Destabilizing | 0.999 | D | 0.665 | prob.neutral | N | 0.493543072 | None | None | N |
| A/W | 0.9893 | likely_pathogenic | 0.9879 | pathogenic | -1.558 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| A/Y | 0.9701 | likely_pathogenic | 0.966 | pathogenic | -1.109 | Destabilizing | 1.0 | D | 0.869 | deleterious | 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.