TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17832	53719;53720;53721	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
N2AB	16191	48796;48797;48798	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
N2A	15264	46015;46016;46017	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
N2B	8767	26524;26525;26526	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
Novex-1	8892	26899;26900;26901	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
Novex-2	8959	27100;27101;27102	chr2:178607108;178607107;178607106	chr2:179471835;179471834;179471833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-17
• Domain position: 69
• Structural Position: 103
• Q(SASA): 0.4185
• 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/A	None	None	0.998	N	0.63	0.516	0.406945738958	gnomAD-4.0.0	2.05392E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.51963E-05	0	3.31565E-05

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	0.2715	likely_benign	0.3079	benign	-0.966	Destabilizing	0.998	D	0.63	neutral	N	0.472080028	None	None	N
E/C	0.9023	likely_pathogenic	0.926	pathogenic	-0.626	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/D	0.4383	ambiguous	0.5392	ambiguous	-1.252	Destabilizing	0.434	N	0.211	neutral	N	0.469433455	None	None	N
E/F	0.9124	likely_pathogenic	0.9334	pathogenic	-0.295	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.4731	ambiguous	0.5278	ambiguous	-1.373	Destabilizing	0.999	D	0.721	prob.delet.	N	0.494565602	None	None	N
E/H	0.8076	likely_pathogenic	0.8595	pathogenic	-0.668	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/I	0.5227	ambiguous	0.6013	pathogenic	0.164	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/K	0.4957	ambiguous	0.5918	pathogenic	-1.072	Destabilizing	0.998	D	0.55	neutral	N	0.518153515	None	None	N
E/L	0.6255	likely_pathogenic	0.6962	pathogenic	0.164	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/M	0.6092	likely_pathogenic	0.6828	pathogenic	0.693	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/N	0.5972	likely_pathogenic	0.6736	pathogenic	-1.501	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/P	0.6701	likely_pathogenic	0.7244	pathogenic	-0.192	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Q	0.277	likely_benign	0.3239	benign	-1.312	Destabilizing	0.999	D	0.665	neutral	D	0.524772843	None	None	N
E/R	0.6438	likely_pathogenic	0.7245	pathogenic	-0.776	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/S	0.4466	ambiguous	0.5033	ambiguous	-1.902	Destabilizing	0.997	D	0.6	neutral	None	None	None	None	N
E/T	0.4044	ambiguous	0.4737	ambiguous	-1.564	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/V	0.3364	likely_benign	0.4073	ambiguous	-0.192	Destabilizing	1.0	D	0.785	deleterious	N	0.481487777	None	None	N
E/W	0.9715	likely_pathogenic	0.9802	pathogenic	-0.086	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/Y	0.848	likely_pathogenic	0.8829	pathogenic	-0.073	Destabilizing	1.0	D	0.775	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.