TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32892	98899;98900;98901	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
N2AB	31251	93976;93977;93978	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
N2A	30324	91195;91196;91197	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
N2B	23827	71704;71705;71706	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
Novex-1	23952	72079;72080;72081	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
Novex-2	24019	72280;72281;72282	chr2:178539391;178539390;178539389	chr2:179404118;179404117;179404116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-127
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.2927
• 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/A	None	None	0.997	N	0.691	0.271	0.259272394797	gnomAD-4.0.0	1.59916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4346E-05	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	0.145	likely_benign	0.1519	benign	-0.251	Destabilizing	0.997	D	0.691	prob.delet.	N	0.491177557	None	None	N
T/C	0.6401	likely_pathogenic	0.6353	pathogenic	-0.323	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
T/D	0.5379	ambiguous	0.5192	ambiguous	0.043	Stabilizing	0.999	D	0.728	deleterious	None	None	None	None	N
T/E	0.5016	ambiguous	0.5181	ambiguous	-0.025	Destabilizing	0.999	D	0.736	deleterious	None	None	None	None	N
T/F	0.3805	ambiguous	0.3939	ambiguous	-0.675	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
T/G	0.4377	ambiguous	0.4196	ambiguous	-0.393	Destabilizing	0.999	D	0.665	prob.neutral	None	None	None	None	N
T/H	0.3911	ambiguous	0.3982	ambiguous	-0.619	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/I	0.2968	likely_benign	0.3079	benign	0.004	Stabilizing	0.999	D	0.709	prob.delet.	N	0.512822266	None	None	N
T/K	0.4248	ambiguous	0.4199	ambiguous	-0.449	Destabilizing	0.999	D	0.734	deleterious	N	0.521153748	None	None	N
T/L	0.1457	likely_benign	0.1405	benign	0.004	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
T/M	0.1218	likely_benign	0.1242	benign	0.016	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/N	0.121	likely_benign	0.121	benign	-0.258	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
T/P	0.1887	likely_benign	0.1916	benign	-0.051	Destabilizing	0.999	D	0.695	prob.delet.	N	0.513168983	None	None	N
T/Q	0.3632	ambiguous	0.3823	ambiguous	-0.459	Destabilizing	0.999	D	0.721	deleterious	None	None	None	None	N
T/R	0.4059	ambiguous	0.4059	ambiguous	-0.141	Destabilizing	0.999	D	0.693	prob.delet.	N	0.46556866	None	None	N
T/S	0.1603	likely_benign	0.1578	benign	-0.434	Destabilizing	0.997	D	0.695	prob.delet.	N	0.480307203	None	None	N
T/V	0.2448	likely_benign	0.2522	benign	-0.051	Destabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
T/W	0.7705	likely_pathogenic	0.7809	pathogenic	-0.716	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
T/Y	0.3583	ambiguous	0.3753	ambiguous	-0.432	Destabilizing	1.0	D	0.736	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.