TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30081	90466;90467;90468	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
N2AB	28440	85543;85544;85545	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
N2A	27513	82762;82763;82764	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
N2B	21016	63271;63272;63273	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
Novex-1	21141	63646;63647;63648	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
Novex-2	21208	63847;63848;63849	chr2:178552659;178552658;178552657	chr2:179417386;179417385;179417384
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-107
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.2014
• 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
G/C	None	None	1.0	D	0.816	0.265	0.488337271218	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85778E-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
G/A	0.1702	likely_benign	0.1335	benign	-0.592	Destabilizing	0.362	N	0.362	neutral	N	0.407580313	None	None	N
G/C	0.4034	ambiguous	0.3128	benign	-0.802	Destabilizing	1.0	D	0.816	deleterious	D	0.522655257	None	None	N
G/D	0.6056	likely_pathogenic	0.4566	ambiguous	-1.221	Destabilizing	0.993	D	0.734	prob.delet.	N	0.472879798	None	None	N
G/E	0.6311	likely_pathogenic	0.4831	ambiguous	-1.29	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
G/F	0.823	likely_pathogenic	0.7388	pathogenic	-0.972	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/H	0.7697	likely_pathogenic	0.6442	pathogenic	-1.238	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/I	0.6245	likely_pathogenic	0.4806	ambiguous	-0.288	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
G/K	0.7512	likely_pathogenic	0.6122	pathogenic	-1.382	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
G/L	0.7121	likely_pathogenic	0.582	pathogenic	-0.288	Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
G/M	0.7235	likely_pathogenic	0.6087	pathogenic	-0.249	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/N	0.6403	likely_pathogenic	0.5011	ambiguous	-1.017	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
G/P	0.9891	likely_pathogenic	0.9789	pathogenic	-0.348	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
G/Q	0.6514	likely_pathogenic	0.5148	ambiguous	-1.196	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
G/R	0.6529	likely_pathogenic	0.514	ambiguous	-1.001	Destabilizing	0.993	D	0.775	deleterious	N	0.499103607	None	None	N
G/S	0.1879	likely_benign	0.1419	benign	-1.189	Destabilizing	0.568	D	0.411	neutral	N	0.456600837	None	None	N
G/T	0.313	likely_benign	0.2346	benign	-1.184	Destabilizing	0.99	D	0.711	prob.delet.	None	None	None	None	N
G/V	0.457	ambiguous	0.3391	benign	-0.348	Destabilizing	0.993	D	0.749	deleterious	N	0.430841174	None	None	N
G/W	0.8139	likely_pathogenic	0.7205	pathogenic	-1.355	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/Y	0.7727	likely_pathogenic	0.6534	pathogenic	-0.941	Destabilizing	1.0	D	0.818	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.