Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22708 | 68347;68348;68349 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| N2AB | 21067 | 63424;63425;63426 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| N2A | 20140 | 60643;60644;60645 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| N2B | 13643 | 41152;41153;41154 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| Novex-1 | 13768 | 41527;41528;41529 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| Novex-2 | 13835 | 41728;41729;41730 | chr2:178578908;178578907;178578906 | chr2:179443635;179443634;179443633 |
| 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/F | rs1195974219  |
-2.221 | 1.0 | D | 0.829 | 0.792 | 0.890525775428 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs1195974219 |
-2.221 | 1.0 | D | 0.829 | 0.792 | 0.890525775428 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | N | None | 0 | 2.28728E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs374300374 |
-2.144 | 1.0 | D | 0.83 | 0.932 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| L/P | rs374300374 |
-2.144 | 1.0 | D | 0.83 | 0.932 | None | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86036E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9845 | likely_pathogenic | 0.9827 | pathogenic | -2.866 | Highly Destabilizing | 0.999 | D | 0.822 | deleterious | None | None | None | None | N |
| L/C | 0.9573 | likely_pathogenic | 0.9592 | pathogenic | -2.146 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -3.368 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/E | 0.9982 | likely_pathogenic | 0.998 | pathogenic | -3.171 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| L/F | 0.8649 | likely_pathogenic | 0.8477 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.635027002 | None | None | N |
| L/G | 0.9951 | likely_pathogenic | 0.995 | pathogenic | -3.398 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| L/H | 0.9941 | likely_pathogenic | 0.9934 | pathogenic | -2.828 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.65185358 | None | None | N |
| L/I | 0.5374 | ambiguous | 0.4932 | ambiguous | -1.322 | Destabilizing | 0.999 | D | 0.826 | deleterious | D | 0.604997399 | None | None | N |
| L/K | 0.9945 | likely_pathogenic | 0.9945 | pathogenic | -2.312 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/M | 0.5185 | ambiguous | 0.5328 | ambiguous | -1.13 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/N | 0.9963 | likely_pathogenic | 0.9962 | pathogenic | -2.597 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/P | 0.9952 | likely_pathogenic | 0.9942 | pathogenic | -1.82 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.65185358 | None | None | N |
| L/Q | 0.9912 | likely_pathogenic | 0.9902 | pathogenic | -2.515 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| L/R | 0.9907 | likely_pathogenic | 0.9905 | pathogenic | -1.886 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.635834219 | None | None | N |
| L/S | 0.9976 | likely_pathogenic | 0.9973 | pathogenic | -3.255 | Highly Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| L/T | 0.9856 | likely_pathogenic | 0.9861 | pathogenic | -2.919 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| L/V | 0.6736 | likely_pathogenic | 0.6305 | pathogenic | -1.82 | Destabilizing | 0.999 | D | 0.837 | deleterious | D | 0.571908577 | None | None | N |
| L/W | 0.9886 | likely_pathogenic | 0.9877 | pathogenic | -2.246 | Highly Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| L/Y | 0.9897 | likely_pathogenic | 0.9892 | pathogenic | -2.022 | Highly Destabilizing | 1.0 | D | 0.801 | 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.