TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19186	57781;57782;57783	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
N2AB	17545	52858;52859;52860	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
N2A	16618	50077;50078;50079	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
N2B	10121	30586;30587;30588	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
Novex-1	10246	30961;30962;30963	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
Novex-2	10313	31162;31163;31164	chr2:178595798;178595797;178595796	chr2:179460525;179460524;179460523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-27
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3822
• Predicted PPI site: I

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/S	None	None	1.0	N	0.839	0.432	0.493628743246	gnomAD-4.0.0	1.38175E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80945E-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
P/A	0.1064	likely_benign	0.1094	benign	-1.042	Destabilizing	1.0	D	0.799	deleterious	N	0.464515022	None	None	I
P/C	0.5769	likely_pathogenic	0.6335	pathogenic	-0.722	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	I
P/D	0.6774	likely_pathogenic	0.7157	pathogenic	-0.671	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
P/E	0.3947	ambiguous	0.4262	ambiguous	-0.748	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/F	0.643	likely_pathogenic	0.6892	pathogenic	-1.011	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	I
P/G	0.5457	ambiguous	0.5629	ambiguous	-1.261	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
P/H	0.293	likely_benign	0.3302	benign	-0.815	Destabilizing	1.0	D	0.885	deleterious	N	0.499552352	None	None	I
P/I	0.4245	ambiguous	0.474	ambiguous	-0.582	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	I
P/K	0.3198	likely_benign	0.3715	ambiguous	-0.814	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
P/L	0.2135	likely_benign	0.2363	benign	-0.582	Destabilizing	1.0	D	0.891	deleterious	N	0.498031415	None	None	I
P/M	0.413	ambiguous	0.4464	ambiguous	-0.436	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
P/N	0.5337	ambiguous	0.5668	pathogenic	-0.484	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
P/Q	0.2149	likely_benign	0.2347	benign	-0.738	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
P/R	0.1912	likely_benign	0.2344	benign	-0.268	Destabilizing	1.0	D	0.907	deleterious	N	0.487435578	None	None	I
P/S	0.2275	likely_benign	0.2394	benign	-0.936	Destabilizing	1.0	D	0.839	deleterious	N	0.497777925	None	None	I
P/T	0.198	likely_benign	0.2153	benign	-0.911	Destabilizing	1.0	D	0.836	deleterious	N	0.498538394	None	None	I
P/V	0.2806	likely_benign	0.3096	benign	-0.699	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/W	0.8286	likely_pathogenic	0.865	pathogenic	-1.091	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
P/Y	0.6423	likely_pathogenic	0.702	pathogenic	-0.815	Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	I

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.