TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21233	63922;63923;63924	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
N2AB	19592	58999;59000;59001	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
N2A	18665	56218;56219;56220	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
N2B	12168	36727;36728;36729	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
Novex-1	12293	37102;37103;37104	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
Novex-2	12360	37303;37304;37305	chr2:178587612;178587611;178587610	chr2:179452339;179452338;179452337
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-123
• Domain position: 57
• Structural Position: 140
• Q(SASA): 0.1493
• 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
I/M	None	None	1.0	D	0.783	0.651	0.704424639576	gnomAD-4.0.0	6.84706E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99751E-07	0	0
I/T	None	None	1.0	D	0.823	0.782	0.873723102753	gnomAD-4.0.0	6.84678E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99743E-07	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
I/A	0.9758	likely_pathogenic	0.9799	pathogenic	-2.394	Highly Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
I/C	0.9654	likely_pathogenic	0.9745	pathogenic	-1.628	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/D	0.9945	likely_pathogenic	0.9949	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
I/E	0.9878	likely_pathogenic	0.989	pathogenic	-2.277	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
I/F	0.67	likely_pathogenic	0.6798	pathogenic	-1.464	Destabilizing	1.0	D	0.822	deleterious	D	0.588972704	None	None	N
I/G	0.9956	likely_pathogenic	0.9964	pathogenic	-2.87	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
I/H	0.9735	likely_pathogenic	0.9761	pathogenic	-2.215	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/K	0.9748	likely_pathogenic	0.9759	pathogenic	-1.928	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
I/L	0.2893	likely_benign	0.317	benign	-1.068	Destabilizing	0.993	D	0.458	neutral	D	0.564168787	None	None	N
I/M	0.4145	ambiguous	0.4507	ambiguous	-0.862	Destabilizing	1.0	D	0.783	deleterious	D	0.612017725	None	None	N
I/N	0.9228	likely_pathogenic	0.9263	pathogenic	-1.991	Destabilizing	1.0	D	0.897	deleterious	D	0.597410994	None	None	N
I/P	0.9945	likely_pathogenic	0.9947	pathogenic	-1.486	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
I/Q	0.9707	likely_pathogenic	0.9738	pathogenic	-1.999	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
I/R	0.9649	likely_pathogenic	0.9656	pathogenic	-1.434	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
I/S	0.954	likely_pathogenic	0.9589	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.62968188	None	None	N
I/T	0.9595	likely_pathogenic	0.9652	pathogenic	-2.409	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.607919124	None	None	N
I/V	0.2273	likely_benign	0.2782	benign	-1.486	Destabilizing	0.993	D	0.411	neutral	D	0.547597676	None	None	N
I/W	0.984	likely_pathogenic	0.9852	pathogenic	-1.76	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
I/Y	0.9397	likely_pathogenic	0.9423	pathogenic	-1.524	Destabilizing	1.0	D	0.831	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.