TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28930	87013;87014;87015	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
N2AB	27289	82090;82091;82092	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
N2A	26362	79309;79310;79311	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
N2B	19865	59818;59819;59820	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
Novex-1	19990	60193;60194;60195	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
Novex-2	20057	60394;60395;60396	chr2:178559344;178559343;178559342	chr2:179424071;179424070;179424069
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-98
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3417
• 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	rs758656233	None	0.979	N	0.396	0.229	0.28058544554	gnomAD-4.0.0	1.37241E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80292E-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	0.0948	likely_benign	0.0999	benign	-1.412	Destabilizing	0.987	D	0.569	neutral	N	0.479709669	None	None	I
P/C	0.5165	ambiguous	0.5602	ambiguous	-0.9	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/D	0.8667	likely_pathogenic	0.8819	pathogenic	-1.101	Destabilizing	0.994	D	0.713	prob.delet.	None	None	None	None	I
P/E	0.7267	likely_pathogenic	0.7491	pathogenic	-1.152	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	I
P/F	0.5299	ambiguous	0.5903	pathogenic	-1.218	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
P/G	0.4485	ambiguous	0.4562	ambiguous	-1.668	Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	I
P/H	0.3644	ambiguous	0.4158	ambiguous	-1.083	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/I	0.5611	ambiguous	0.6355	pathogenic	-0.834	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/K	0.7871	likely_pathogenic	0.8049	pathogenic	-1.098	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
P/L	0.2579	likely_benign	0.2958	benign	-0.834	Destabilizing	1.0	D	0.777	deleterious	N	0.515184164	None	None	I
P/M	0.5063	ambiguous	0.5598	ambiguous	-0.6	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
P/N	0.6968	likely_pathogenic	0.7345	pathogenic	-0.803	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
P/Q	0.4116	ambiguous	0.4383	ambiguous	-1.065	Destabilizing	1.0	D	0.791	deleterious	D	0.528314896	None	None	I
P/R	0.5748	likely_pathogenic	0.5968	pathogenic	-0.475	Destabilizing	1.0	D	0.79	deleterious	N	0.504930722	None	None	I
P/S	0.2037	likely_benign	0.2105	benign	-1.296	Destabilizing	0.979	D	0.396	neutral	N	0.474545109	None	None	I
P/T	0.2238	likely_benign	0.24	benign	-1.249	Destabilizing	0.999	D	0.727	prob.delet.	N	0.509957151	None	None	I
P/V	0.3885	ambiguous	0.4439	ambiguous	-0.992	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/W	0.7322	likely_pathogenic	0.7884	pathogenic	-1.294	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
P/Y	0.5646	likely_pathogenic	0.6386	pathogenic	-1.047	Destabilizing	1.0	D	0.83	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.