TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1856	5791;5792;5793	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
N2AB	1856	5791;5792;5793	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
N2A	1856	5791;5792;5793	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
N2B	1810	5653;5654;5655	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
Novex-1	1810	5653;5654;5655	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
Novex-2	1810	5653;5654;5655	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023
Novex-3	1856	5791;5792;5793	chr2:178776298;178776297;178776296	chr2:179641025;179641024;179641023

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-9
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3395
• Predicted PPI site: N

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
E/K	rs1315454944	None	0.896	N	0.383	0.191	0.156986980423	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
E/K	rs1315454944	None	0.896	N	0.383	0.191	0.156986980423	gnomAD-4.0.0	1.05332E-05	None	None	None	None	N	None	1.33483E-05	0	None	0	0	None	0	0	1.35593E-05	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
E/A	0.7235	likely_pathogenic	0.7054	pathogenic	-0.575	Destabilizing	0.896	D	0.357	neutral	N	0.422689735	None	None	N
E/C	0.99	likely_pathogenic	0.9889	pathogenic	-0.049	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
E/D	0.2776	likely_benign	0.2995	benign	-0.56	Destabilizing	0.011	N	0.155	neutral	N	0.425115529	None	None	N
E/F	0.9875	likely_pathogenic	0.9867	pathogenic	-0.447	Destabilizing	0.996	D	0.535	neutral	None	None	None	None	N
E/G	0.6619	likely_pathogenic	0.6317	pathogenic	-0.81	Destabilizing	0.896	D	0.403	neutral	N	0.42625852	None	None	N
E/H	0.9445	likely_pathogenic	0.9403	pathogenic	-0.44	Destabilizing	0.988	D	0.345	neutral	None	None	None	None	N
E/I	0.9554	likely_pathogenic	0.9569	pathogenic	0.023	Stabilizing	0.988	D	0.532	neutral	None	None	None	None	N
E/K	0.7708	likely_pathogenic	0.7554	pathogenic	0.136	Stabilizing	0.896	D	0.383	neutral	N	0.426106871	None	None	N
E/L	0.953	likely_pathogenic	0.9498	pathogenic	0.023	Stabilizing	0.988	D	0.475	neutral	None	None	None	None	N
E/M	0.9326	likely_pathogenic	0.9296	pathogenic	0.309	Stabilizing	0.999	D	0.498	neutral	None	None	None	None	N
E/N	0.7088	likely_pathogenic	0.7154	pathogenic	-0.206	Destabilizing	0.132	N	0.269	neutral	None	None	None	None	N
E/P	0.9978	likely_pathogenic	0.9971	pathogenic	-0.155	Destabilizing	0.988	D	0.347	neutral	None	None	None	None	N
E/Q	0.5491	ambiguous	0.5222	ambiguous	-0.168	Destabilizing	0.946	D	0.394	neutral	N	0.42979175	None	None	N
E/R	0.8731	likely_pathogenic	0.8596	pathogenic	0.294	Stabilizing	0.988	D	0.351	neutral	None	None	None	None	N
E/S	0.7135	likely_pathogenic	0.6928	pathogenic	-0.387	Destabilizing	0.919	D	0.35	neutral	None	None	None	None	N
E/T	0.8364	likely_pathogenic	0.8368	pathogenic	-0.196	Destabilizing	0.919	D	0.392	neutral	None	None	None	None	N
E/V	0.8689	likely_pathogenic	0.8688	pathogenic	-0.155	Destabilizing	0.984	D	0.438	neutral	N	0.469850242	None	None	N
E/W	0.9972	likely_pathogenic	0.9968	pathogenic	-0.274	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
E/Y	0.9724	likely_pathogenic	0.9722	pathogenic	-0.201	Destabilizing	0.996	D	0.503	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.