TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32749	98470;98471;98472	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
N2AB	31108	93547;93548;93549	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
N2A	30181	90766;90767;90768	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
N2B	23684	71275;71276;71277	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
Novex-1	23809	71650;71651;71652	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
Novex-2	23876	71851;71852;71853	chr2:178539820;178539819;178539818	chr2:179404547;179404546;179404545
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-155
• Domain position: 42
• Structural Position: 121
• Q(SASA): 0.2704
• 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
A/T	rs1693506739	None	1.0	N	0.704	0.317	0.542675667512	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.6632	likely_pathogenic	0.675	pathogenic	-0.924	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
A/D	0.972	likely_pathogenic	0.9768	pathogenic	-1.375	Destabilizing	1.0	D	0.78	deleterious	D	0.530384598	None	None	N
A/E	0.9621	likely_pathogenic	0.9645	pathogenic	-1.344	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/F	0.8753	likely_pathogenic	0.8873	pathogenic	-0.82	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/G	0.2585	likely_benign	0.2558	benign	-1.144	Destabilizing	1.0	D	0.568	neutral	N	0.501947203	None	None	N
A/H	0.9683	likely_pathogenic	0.9711	pathogenic	-1.445	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/I	0.7925	likely_pathogenic	0.8315	pathogenic	-0.101	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/K	0.9865	likely_pathogenic	0.9867	pathogenic	-1.318	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/L	0.7644	likely_pathogenic	0.7725	pathogenic	-0.101	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/M	0.7889	likely_pathogenic	0.8078	pathogenic	-0.161	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
A/N	0.9362	likely_pathogenic	0.946	pathogenic	-1.203	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/P	0.9648	likely_pathogenic	0.9723	pathogenic	-0.3	Destabilizing	1.0	D	0.796	deleterious	D	0.525536139	None	None	N
A/Q	0.9531	likely_pathogenic	0.9495	pathogenic	-1.247	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/R	0.9713	likely_pathogenic	0.9703	pathogenic	-1.075	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/S	0.2489	likely_benign	0.287	benign	-1.542	Destabilizing	1.0	D	0.593	neutral	N	0.500061691	None	None	N
A/T	0.4656	ambiguous	0.5156	ambiguous	-1.404	Destabilizing	1.0	D	0.704	prob.neutral	N	0.492346285	None	None	N
A/V	0.4747	ambiguous	0.5246	ambiguous	-0.3	Destabilizing	1.0	D	0.635	neutral	N	0.459751077	None	None	N
A/W	0.9833	likely_pathogenic	0.9851	pathogenic	-1.315	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/Y	0.9292	likely_pathogenic	0.9408	pathogenic	-0.833	Destabilizing	1.0	D	0.794	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.