TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7094	21505;21506;21507	chr2:178723979;178723978;178723977	chr2:179588706;179588705;179588704
N2AB	6777	20554;20555;20556	chr2:178723979;178723978;178723977	chr2:179588706;179588705;179588704
N2A	5850	17773;17774;17775	chr2:178723979;178723978;178723977	chr2:179588706;179588705;179588704
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-55
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4088
• 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
F/S	None	None	0.003	N	0.493	0.286	0.605748623547	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
F/A	0.6515	likely_pathogenic	0.6732	pathogenic	-1.728	Destabilizing	0.404	N	0.657	neutral	None	None	None	None	N
F/C	0.3904	ambiguous	0.4184	ambiguous	-0.878	Destabilizing	0.965	D	0.735	prob.delet.	N	0.505709596	None	None	N
F/D	0.89	likely_pathogenic	0.9154	pathogenic	0.258	Stabilizing	0.826	D	0.738	prob.delet.	None	None	None	None	N
F/E	0.8976	likely_pathogenic	0.9239	pathogenic	0.301	Stabilizing	0.704	D	0.713	prob.delet.	None	None	None	None	N
F/G	0.8538	likely_pathogenic	0.8721	pathogenic	-2.015	Highly Destabilizing	0.404	N	0.682	prob.neutral	None	None	None	None	N
F/H	0.713	likely_pathogenic	0.7453	pathogenic	-0.432	Destabilizing	0.973	D	0.661	neutral	None	None	None	None	N
F/I	0.2096	likely_benign	0.2288	benign	-0.915	Destabilizing	0.338	N	0.582	neutral	D	0.535174343	None	None	N
F/K	0.9033	likely_pathogenic	0.9298	pathogenic	-0.708	Destabilizing	0.704	D	0.705	prob.neutral	None	None	None	None	N
F/L	0.819	likely_pathogenic	0.8106	pathogenic	-0.915	Destabilizing	0.003	N	0.3	neutral	N	0.479513061	None	None	N
F/M	0.5592	ambiguous	0.5802	pathogenic	-0.709	Destabilizing	0.826	D	0.638	neutral	None	None	None	None	N
F/N	0.7696	likely_pathogenic	0.8009	pathogenic	-0.631	Destabilizing	0.704	D	0.741	deleterious	None	None	None	None	N
F/P	0.984	likely_pathogenic	0.9883	pathogenic	-1.173	Destabilizing	0.826	D	0.744	deleterious	None	None	None	None	N
F/Q	0.8494	likely_pathogenic	0.8774	pathogenic	-0.693	Destabilizing	0.826	D	0.746	deleterious	None	None	None	None	N
F/R	0.7935	likely_pathogenic	0.8374	pathogenic	-0.14	Destabilizing	0.826	D	0.741	deleterious	None	None	None	None	N
F/S	0.5242	ambiguous	0.5419	ambiguous	-1.496	Destabilizing	0.003	N	0.493	neutral	N	0.506467589	None	None	N
F/T	0.6351	likely_pathogenic	0.6588	pathogenic	-1.359	Destabilizing	0.404	N	0.687	prob.neutral	None	None	None	None	N
F/V	0.2072	likely_benign	0.2212	benign	-1.173	Destabilizing	0.338	N	0.626	neutral	N	0.49815475	None	None	N
F/W	0.5944	likely_pathogenic	0.6193	pathogenic	-0.332	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	N
F/Y	0.2094	likely_benign	0.2186	benign	-0.446	Destabilizing	0.674	D	0.601	neutral	N	0.469565426	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.