TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4884	14875;14876;14877	chr2:178735796;178735795;178735794	chr2:179600523;179600522;179600521
N2AB	4567	13924;13925;13926	chr2:178735796;178735795;178735794	chr2:179600523;179600522;179600521
N2A	3640	11143;11144;11145	chr2:178735796;178735795;178735794	chr2:179600523;179600522;179600521
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-31
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2144
• 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/V	None	None	None	N	0.345	0.092	0.156986980423	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.7445	likely_pathogenic	0.6353	pathogenic	-2.43	Highly Destabilizing	0.072	N	0.641	neutral	None	None	None	None	N
I/C	0.864	likely_pathogenic	0.8059	pathogenic	-1.692	Destabilizing	0.909	D	0.72	prob.delet.	None	None	None	None	N
I/D	0.9793	likely_pathogenic	0.9613	pathogenic	-2.404	Highly Destabilizing	0.726	D	0.795	deleterious	None	None	None	None	N
I/E	0.9593	likely_pathogenic	0.9333	pathogenic	-2.209	Highly Destabilizing	0.726	D	0.782	deleterious	None	None	None	None	N
I/F	0.5439	ambiguous	0.4277	ambiguous	-1.379	Destabilizing	0.497	N	0.587	neutral	D	0.619400411	None	None	N
I/G	0.9287	likely_pathogenic	0.8777	pathogenic	-2.929	Highly Destabilizing	0.726	D	0.768	deleterious	None	None	None	None	N
I/H	0.9468	likely_pathogenic	0.9098	pathogenic	-2.283	Highly Destabilizing	0.968	D	0.793	deleterious	None	None	None	None	N
I/K	0.922	likely_pathogenic	0.8812	pathogenic	-1.677	Destabilizing	0.726	D	0.781	deleterious	None	None	None	None	N
I/L	0.2118	likely_benign	0.1573	benign	-1.002	Destabilizing	0.025	N	0.465	neutral	N	0.52081098	None	None	N
I/M	0.2626	likely_benign	0.2052	benign	-1.058	Destabilizing	0.497	N	0.621	neutral	D	0.620411052	None	None	N
I/N	0.7911	likely_pathogenic	0.7161	pathogenic	-1.892	Destabilizing	0.859	D	0.801	deleterious	D	0.621055801	None	None	N
I/P	0.9151	likely_pathogenic	0.8788	pathogenic	-1.458	Destabilizing	0.89	D	0.801	deleterious	None	None	None	None	N
I/Q	0.9324	likely_pathogenic	0.8914	pathogenic	-1.802	Destabilizing	0.89	D	0.801	deleterious	None	None	None	None	N
I/R	0.8838	likely_pathogenic	0.8338	pathogenic	-1.4	Destabilizing	0.726	D	0.801	deleterious	None	None	None	None	N
I/S	0.7685	likely_pathogenic	0.682	pathogenic	-2.61	Highly Destabilizing	0.497	N	0.73	prob.delet.	D	0.620528145	None	None	N
I/T	0.616	likely_pathogenic	0.5285	ambiguous	-2.282	Highly Destabilizing	0.124	N	0.64	neutral	D	0.579033094	None	None	N
I/V	0.0792	likely_benign	0.0666	benign	-1.458	Destabilizing	None	N	0.345	neutral	N	0.350329813	None	None	N
I/W	0.979	likely_pathogenic	0.9644	pathogenic	-1.679	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
I/Y	0.8945	likely_pathogenic	0.8345	pathogenic	-1.421	Destabilizing	0.726	D	0.72	prob.delet.	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.