TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24706	74341;74342;74343	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
N2AB	23065	69418;69419;69420	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
N2A	22138	66637;66638;66639	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
N2B	15641	47146;47147;47148	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
Novex-1	15766	47521;47522;47523	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
Novex-2	15833	47722;47723;47724	chr2:178572016;178572015;178572014	chr2:179436743;179436742;179436741
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: Fn3-67
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.3601
• 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/S	None	None	0.546	N	0.583	0.273	0.243398259712	gnomAD-4.0.0	2.05342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69889E-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	0.1486	likely_benign	0.1541	benign	-0.694	Destabilizing	0.26	N	0.512	neutral	N	0.465992598	None	None	N
P/C	0.8308	likely_pathogenic	0.8354	pathogenic	-0.789	Destabilizing	0.987	D	0.787	deleterious	None	None	None	None	N
P/D	0.8227	likely_pathogenic	0.8098	pathogenic	-0.387	Destabilizing	0.101	N	0.606	neutral	None	None	None	None	N
P/E	0.7061	likely_pathogenic	0.7087	pathogenic	-0.458	Destabilizing	0.003	N	0.32	neutral	None	None	None	None	N
P/F	0.8764	likely_pathogenic	0.8659	pathogenic	-0.651	Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
P/G	0.5829	likely_pathogenic	0.573	pathogenic	-0.885	Destabilizing	0.89	D	0.675	prob.neutral	None	None	None	None	N
P/H	0.5419	ambiguous	0.5256	ambiguous	-0.334	Destabilizing	0.991	D	0.724	deleterious	None	None	None	None	N
P/I	0.768	likely_pathogenic	0.7564	pathogenic	-0.317	Destabilizing	0.976	D	0.826	deleterious	None	None	None	None	N
P/K	0.7523	likely_pathogenic	0.7436	pathogenic	-0.686	Destabilizing	0.851	D	0.64	neutral	None	None	None	None	N
P/L	0.3532	ambiguous	0.3463	ambiguous	-0.317	Destabilizing	0.938	D	0.696	prob.delet.	N	0.477095414	None	None	N
P/M	0.6831	likely_pathogenic	0.663	pathogenic	-0.472	Destabilizing	0.991	D	0.731	deleterious	None	None	None	None	N
P/N	0.644	likely_pathogenic	0.6051	pathogenic	-0.486	Destabilizing	0.833	D	0.761	deleterious	None	None	None	None	N
P/Q	0.474	ambiguous	0.4562	ambiguous	-0.675	Destabilizing	0.85	D	0.655	prob.neutral	N	0.494531787	None	None	N
P/R	0.5867	likely_pathogenic	0.5858	pathogenic	-0.169	Destabilizing	0.968	D	0.772	deleterious	N	0.497165133	None	None	N
P/S	0.2522	likely_benign	0.238	benign	-0.903	Destabilizing	0.546	D	0.583	neutral	N	0.463487837	None	None	N
P/T	0.2545	likely_benign	0.2347	benign	-0.865	Destabilizing	0.008	N	0.322	neutral	N	0.482415013	None	None	N
P/V	0.5715	likely_pathogenic	0.5618	ambiguous	-0.407	Destabilizing	0.778	D	0.667	prob.neutral	None	None	None	None	N
P/W	0.9411	likely_pathogenic	0.9363	pathogenic	-0.747	Destabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	N
P/Y	0.8743	likely_pathogenic	0.8654	pathogenic	-0.466	Destabilizing	0.999	D	0.793	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.