TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20838	62737;62738;62739	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
N2AB	19197	57814;57815;57816	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
N2A	18270	55033;55034;55035	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
N2B	11773	35542;35543;35544	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
Novex-1	11898	35917;35918;35919	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
Novex-2	11965	36118;36119;36120	chr2:178589213;178589212;178589211	chr2:179453940;179453939;179453938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-122
• Domain position: 70
• Structural Position: 149
• Q(SASA): 0.2539
• 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
D/N	None	None	1.0	D	0.783	0.689	0.762446115887	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79911E-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
D/A	0.9861	likely_pathogenic	0.9791	pathogenic	-0.209	Destabilizing	1.0	D	0.867	deleterious	D	0.641086514	None	None	N
D/C	0.987	likely_pathogenic	0.985	pathogenic	-0.031	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
D/E	0.9248	likely_pathogenic	0.9128	pathogenic	-0.617	Destabilizing	1.0	D	0.6	neutral	D	0.602497179	None	None	N
D/F	0.9966	likely_pathogenic	0.9953	pathogenic	0.4	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
D/G	0.9913	likely_pathogenic	0.9879	pathogenic	-0.578	Destabilizing	1.0	D	0.793	deleterious	D	0.657307679	None	None	N
D/H	0.946	likely_pathogenic	0.9518	pathogenic	0.234	Stabilizing	1.0	D	0.835	deleterious	D	0.578573502	None	None	N
D/I	0.9969	likely_pathogenic	0.9961	pathogenic	0.763	Stabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
D/K	0.9945	likely_pathogenic	0.9942	pathogenic	0.165	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/L	0.9962	likely_pathogenic	0.9949	pathogenic	0.763	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/M	0.9979	likely_pathogenic	0.9975	pathogenic	1.043	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/N	0.9003	likely_pathogenic	0.8949	pathogenic	-0.569	Destabilizing	1.0	D	0.783	deleterious	D	0.629953329	None	None	N
D/P	0.9992	likely_pathogenic	0.999	pathogenic	0.466	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/Q	0.9864	likely_pathogenic	0.9853	pathogenic	-0.384	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
D/R	0.994	likely_pathogenic	0.9935	pathogenic	0.356	Stabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
D/S	0.9628	likely_pathogenic	0.9518	pathogenic	-0.733	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
D/T	0.9925	likely_pathogenic	0.9898	pathogenic	-0.406	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
D/V	0.991	likely_pathogenic	0.9879	pathogenic	0.466	Stabilizing	1.0	D	0.867	deleterious	D	0.641691927	None	None	N
D/W	0.9985	likely_pathogenic	0.998	pathogenic	0.634	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/Y	0.9718	likely_pathogenic	0.9639	pathogenic	0.693	Stabilizing	1.0	D	0.871	deleterious	D	0.657509484	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.