TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17878	53857;53858;53859	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
N2AB	16237	48934;48935;48936	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
N2A	15310	46153;46154;46155	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
N2B	8813	26662;26663;26664	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
Novex-1	8938	27037;27038;27039	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
Novex-2	9005	27238;27239;27240	chr2:178605663;178605662;178605661	chr2:179470390;179470389;179470388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-18
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1786
• 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
T/I	None	None	0.984	N	0.727	0.31	0.462461958149	gnomAD-4.0.0	1.60683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89039E-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
T/A	0.1947	likely_benign	0.1677	benign	-1.13	Destabilizing	0.64	D	0.449	neutral	N	0.489564191	None	None	N
T/C	0.5799	likely_pathogenic	0.5441	ambiguous	-0.895	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
T/D	0.7971	likely_pathogenic	0.7784	pathogenic	-0.945	Destabilizing	0.919	D	0.664	neutral	None	None	None	None	N
T/E	0.7601	likely_pathogenic	0.7266	pathogenic	-0.829	Destabilizing	0.919	D	0.659	neutral	None	None	None	None	N
T/F	0.5861	likely_pathogenic	0.5767	pathogenic	-0.919	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
T/G	0.395	ambiguous	0.354	ambiguous	-1.489	Destabilizing	0.851	D	0.611	neutral	None	None	None	None	N
T/H	0.4909	ambiguous	0.4646	ambiguous	-1.637	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
T/I	0.773	likely_pathogenic	0.7383	pathogenic	-0.225	Destabilizing	0.984	D	0.727	prob.delet.	N	0.48108293	None	None	N
T/K	0.6619	likely_pathogenic	0.6447	pathogenic	-0.734	Destabilizing	0.919	D	0.66	neutral	None	None	None	None	N
T/L	0.4242	ambiguous	0.3939	ambiguous	-0.225	Destabilizing	0.919	D	0.611	neutral	None	None	None	None	N
T/M	0.2327	likely_benign	0.2081	benign	-0.083	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
T/N	0.3118	likely_benign	0.2828	benign	-1.1	Destabilizing	0.896	D	0.569	neutral	N	0.506341798	None	None	N
T/P	0.9776	likely_pathogenic	0.9708	pathogenic	-0.494	Destabilizing	0.984	D	0.725	prob.delet.	N	0.487666295	None	None	N
T/Q	0.5332	ambiguous	0.4981	ambiguous	-1.089	Destabilizing	0.988	D	0.738	prob.delet.	None	None	None	None	N
T/R	0.5988	likely_pathogenic	0.5669	pathogenic	-0.704	Destabilizing	0.976	D	0.734	prob.delet.	None	None	None	None	N
T/S	0.1094	likely_benign	0.0981	benign	-1.397	Destabilizing	0.046	N	0.211	neutral	N	0.382524366	None	None	N
T/V	0.5368	ambiguous	0.497	ambiguous	-0.494	Destabilizing	0.919	D	0.536	neutral	None	None	None	None	N
T/W	0.8864	likely_pathogenic	0.881	pathogenic	-0.906	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
T/Y	0.587	likely_pathogenic	0.582	pathogenic	-0.611	Destabilizing	0.996	D	0.775	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.