TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21776	65551;65552;65553	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
N2AB	20135	60628;60629;60630	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
N2A	19208	57847;57848;57849	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
N2B	12711	38356;38357;38358	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
Novex-1	12836	38731;38732;38733	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
Novex-2	12903	38932;38933;38934	chr2:178583856;178583855;178583854	chr2:179448583;179448582;179448581
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-46
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0727
• 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
L/M	None	None	1.0	N	0.766	0.43	0.683172565385	gnomAD-4.0.0	1.60625E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88224E-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
L/A	0.95	likely_pathogenic	0.9439	pathogenic	-2.466	Highly Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
L/C	0.897	likely_pathogenic	0.8839	pathogenic	-1.461	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.062	Highly Destabilizing	1.0	D	0.947	deleterious	None	None	None	None	N
L/E	0.9968	likely_pathogenic	0.9972	pathogenic	-2.736	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
L/F	0.6498	likely_pathogenic	0.6406	pathogenic	-1.44	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/G	0.9926	likely_pathogenic	0.9925	pathogenic	-3.081	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/H	0.9919	likely_pathogenic	0.9932	pathogenic	-2.879	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/I	0.179	likely_benign	0.1431	benign	-0.625	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
L/K	0.9937	likely_pathogenic	0.9953	pathogenic	-1.783	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/M	0.2932	likely_benign	0.2623	benign	-0.712	Destabilizing	1.0	D	0.766	deleterious	N	0.519419304	None	None	N
L/N	0.9968	likely_pathogenic	0.997	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.948	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9973	pathogenic	-1.228	Destabilizing	1.0	D	0.948	deleterious	D	0.554413273	None	None	N
L/Q	0.9843	likely_pathogenic	0.9872	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.947	deleterious	D	0.554413273	None	None	N
L/R	0.9865	likely_pathogenic	0.9901	pathogenic	-1.931	Destabilizing	1.0	D	0.937	deleterious	D	0.554413273	None	None	N
L/S	0.9938	likely_pathogenic	0.9936	pathogenic	-3.028	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/T	0.9695	likely_pathogenic	0.9665	pathogenic	-2.535	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/V	0.182	likely_benign	0.1458	benign	-1.228	Destabilizing	0.999	D	0.555	neutral	N	0.477439306	None	None	N
L/W	0.9734	likely_pathogenic	0.9784	pathogenic	-1.889	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/Y	0.9774	likely_pathogenic	0.9784	pathogenic	-1.608	Destabilizing	1.0	D	0.863	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.