TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30738	92437;92438;92439	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
N2AB	29097	87514;87515;87516	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
N2A	28170	84733;84734;84735	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
N2B	21673	65242;65243;65244	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
Novex-1	21798	65617;65618;65619	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
Novex-2	21865	65818;65819;65820	chr2:178549414;178549413;178549412	chr2:179414141;179414140;179414139
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: Fn3-112
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0669
• 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/R	None	None	0.984	D	0.844	0.625	0.848371208543	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-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	0.8915	likely_pathogenic	0.9052	pathogenic	-2.724	Highly Destabilizing	0.851	D	0.733	prob.delet.	None	None	None	None	N
L/C	0.8255	likely_pathogenic	0.8702	pathogenic	-1.855	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.393	Highly Destabilizing	0.988	D	0.883	deleterious	None	None	None	None	N
L/E	0.9954	likely_pathogenic	0.9958	pathogenic	-3.057	Highly Destabilizing	0.988	D	0.848	deleterious	None	None	None	None	N
L/F	0.7859	likely_pathogenic	0.8195	pathogenic	-1.61	Destabilizing	0.976	D	0.665	neutral	None	None	None	None	N
L/G	0.9903	likely_pathogenic	0.9919	pathogenic	-3.353	Highly Destabilizing	0.988	D	0.842	deleterious	None	None	None	None	N
L/H	0.9923	likely_pathogenic	0.9929	pathogenic	-3.134	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
L/I	0.1019	likely_benign	0.1003	benign	-0.829	Destabilizing	0.702	D	0.609	neutral	None	None	None	None	N
L/K	0.9953	likely_pathogenic	0.995	pathogenic	-2.026	Highly Destabilizing	0.988	D	0.792	deleterious	None	None	None	None	N
L/M	0.2707	likely_benign	0.287	benign	-1.017	Destabilizing	0.64	D	0.529	neutral	N	0.512605222	None	None	N
L/N	0.9959	likely_pathogenic	0.996	pathogenic	-2.769	Highly Destabilizing	0.988	D	0.88	deleterious	None	None	None	None	N
L/P	0.997	likely_pathogenic	0.9968	pathogenic	-1.452	Destabilizing	0.995	D	0.883	deleterious	D	0.554689535	None	None	N
L/Q	0.9834	likely_pathogenic	0.9847	pathogenic	-2.374	Highly Destabilizing	0.984	D	0.847	deleterious	D	0.554689535	None	None	N
L/R	0.9895	likely_pathogenic	0.9902	pathogenic	-2.159	Highly Destabilizing	0.984	D	0.844	deleterious	D	0.554689535	None	None	N
L/S	0.9878	likely_pathogenic	0.9895	pathogenic	-3.315	Highly Destabilizing	0.952	D	0.785	deleterious	None	None	None	None	N
L/T	0.9241	likely_pathogenic	0.9338	pathogenic	-2.807	Highly Destabilizing	0.261	N	0.601	neutral	None	None	None	None	N
L/V	0.085	likely_benign	0.0928	benign	-1.452	Destabilizing	0.026	N	0.312	neutral	N	0.44606413	None	None	N
L/W	0.9872	likely_pathogenic	0.9896	pathogenic	-2.038	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
L/Y	0.9838	likely_pathogenic	0.9857	pathogenic	-1.819	Destabilizing	0.988	D	0.729	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.