Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19595 | 59008;59009;59010 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| N2AB | 17954 | 54085;54086;54087 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| N2A | 17027 | 51304;51305;51306 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| N2B | 10530 | 31813;31814;31815 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| Novex-1 | 10655 | 32188;32189;32190 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| Novex-2 | 10722 | 32389;32390;32391 | chr2:178593425;178593424;178593423 | chr2:179458152;179458151;179458150 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs1354326243  |
-0.796 | 0.999 | N | 0.841 | 0.478 | 0.506006782367 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| S/F | rs1354326243 |
-0.796 | 0.999 | N | 0.841 | 0.478 | 0.506006782367 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/F | rs1354326243 |
-0.796 | 0.999 | N | 0.841 | 0.478 | 0.506006782367 | gnomAD-4.0.0 | 5.12789E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57712E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1098 | likely_benign | 0.1094 | benign | -0.461 | Destabilizing | 0.948 | D | 0.422 | neutral | N | 0.480254145 | None | None | N |
| S/C | 0.1134 | likely_benign | 0.1032 | benign | -0.858 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.503677998 | None | None | N |
| S/D | 0.7113 | likely_pathogenic | 0.7211 | pathogenic | -1.879 | Destabilizing | 0.992 | D | 0.527 | neutral | None | None | None | None | N |
| S/E | 0.7044 | likely_pathogenic | 0.7384 | pathogenic | -1.82 | Destabilizing | 0.992 | D | 0.527 | neutral | None | None | None | None | N |
| S/F | 0.2064 | likely_benign | 0.2185 | benign | -0.736 | Destabilizing | 0.999 | D | 0.841 | deleterious | N | 0.499639074 | None | None | N |
| S/G | 0.134 | likely_benign | 0.1225 | benign | -0.712 | Destabilizing | 0.992 | D | 0.454 | neutral | None | None | None | None | N |
| S/H | 0.3815 | ambiguous | 0.3737 | ambiguous | -1.24 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| S/I | 0.3374 | likely_benign | 0.3664 | ambiguous | 0.107 | Stabilizing | 0.995 | D | 0.83 | deleterious | None | None | None | None | N |
| S/K | 0.8476 | likely_pathogenic | 0.8416 | pathogenic | -0.715 | Destabilizing | 0.983 | D | 0.525 | neutral | None | None | None | None | N |
| S/L | 0.1708 | likely_benign | 0.1744 | benign | 0.107 | Stabilizing | 0.983 | D | 0.691 | prob.neutral | None | None | None | None | N |
| S/M | 0.2306 | likely_benign | 0.2453 | benign | 0.241 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| S/N | 0.2582 | likely_benign | 0.2575 | benign | -1.179 | Destabilizing | 0.992 | D | 0.532 | neutral | None | None | None | None | N |
| S/P | 0.9916 | likely_pathogenic | 0.9911 | pathogenic | -0.05 | Destabilizing | 0.999 | D | 0.787 | deleterious | D | 0.549014315 | None | None | N |
| S/Q | 0.6257 | likely_pathogenic | 0.6371 | pathogenic | -1.328 | Destabilizing | 0.999 | D | 0.67 | neutral | None | None | None | None | N |
| S/R | 0.7647 | likely_pathogenic | 0.7408 | pathogenic | -0.618 | Destabilizing | 0.998 | D | 0.809 | deleterious | None | None | None | None | N |
| S/T | 0.1104 | likely_benign | 0.1081 | benign | -0.875 | Destabilizing | 0.37 | N | 0.355 | neutral | N | 0.510713041 | None | None | N |
| S/V | 0.3315 | likely_benign | 0.3537 | ambiguous | -0.05 | Destabilizing | 0.995 | D | 0.749 | deleterious | None | None | None | None | N |
| S/W | 0.4828 | ambiguous | 0.4669 | ambiguous | -0.924 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| S/Y | 0.2091 | likely_benign | 0.2135 | benign | -0.502 | Destabilizing | 0.999 | D | 0.839 | deleterious | N | 0.502410551 | 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.