TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14769	44530;44531;44532	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
N2AB	13128	39607;39608;39609	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
N2A	12201	36826;36827;36828	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
N2B	5704	17335;17336;17337	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
Novex-1	5829	17710;17711;17712	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
Novex-2	5896	17911;17912;17913	chr2:178629420;178629419;178629418	chr2:179494147;179494146;179494145
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-99
• Domain position: 5
• Structural Position: 7
• Q(SASA): 0.559
• 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
P/T	None	None	1.0	D	0.8	0.493	0.605022544966	gnomAD-4.0.0	1.59324E-06	None	None	None	None	N	None	0	0	None	0	2.78272E-05	None	0	0	0	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
P/A	0.2338	likely_benign	0.1907	benign	-1.037	Destabilizing	1.0	D	0.741	deleterious	D	0.570714074	None	None	N
P/C	0.8766	likely_pathogenic	0.836	pathogenic	-0.613	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/D	0.8051	likely_pathogenic	0.7204	pathogenic	-0.956	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/E	0.6269	likely_pathogenic	0.5124	ambiguous	-1.011	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/F	0.8839	likely_pathogenic	0.8186	pathogenic	-0.918	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
P/G	0.623	likely_pathogenic	0.5096	ambiguous	-1.274	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/H	0.4887	ambiguous	0.3695	ambiguous	-0.823	Destabilizing	1.0	D	0.721	prob.delet.	D	0.533807268	None	None	N
P/I	0.7742	likely_pathogenic	0.7342	pathogenic	-0.518	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
P/K	0.6311	likely_pathogenic	0.5502	ambiguous	-0.949	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/L	0.3893	ambiguous	0.3379	benign	-0.518	Destabilizing	1.0	D	0.788	deleterious	D	0.583622178	None	None	N
P/M	0.7252	likely_pathogenic	0.6643	pathogenic	-0.4	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
P/N	0.7333	likely_pathogenic	0.6205	pathogenic	-0.659	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/Q	0.3927	ambiguous	0.311	benign	-0.881	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/R	0.4503	ambiguous	0.3646	ambiguous	-0.372	Destabilizing	1.0	D	0.768	deleterious	D	0.548106436	None	None	N
P/S	0.3754	ambiguous	0.2727	benign	-1.045	Destabilizing	1.0	D	0.805	deleterious	D	0.547607016	None	None	N
P/T	0.3647	ambiguous	0.2916	benign	-1.002	Destabilizing	1.0	D	0.8	deleterious	D	0.5718786	None	None	N
P/V	0.598	likely_pathogenic	0.5402	ambiguous	-0.656	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/W	0.9308	likely_pathogenic	0.892	pathogenic	-1.07	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
P/Y	0.8111	likely_pathogenic	0.7292	pathogenic	-0.788	Destabilizing	1.0	D	0.735	prob.delet.	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.