TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27435	82528;82529;82530	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
N2AB	25794	77605;77606;77607	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
N2A	24867	74824;74825;74826	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
N2B	18370	55333;55334;55335	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
Novex-1	18495	55708;55709;55710	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
Novex-2	18562	55909;55910;55911	chr2:178563829;178563828;178563827	chr2:179428556;179428555;179428554
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-87
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6195
• 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/I	rs1060500432	None	0.979	N	0.459	0.253	0.379193981924	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9109	likely_pathogenic	0.9102	pathogenic	-1.469	Destabilizing	0.968	D	0.54	neutral	None	None	None	None	N
L/C	0.9342	likely_pathogenic	0.9441	pathogenic	-0.807	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
L/D	0.9932	likely_pathogenic	0.9946	pathogenic	-0.675	Destabilizing	0.995	D	0.733	prob.delet.	None	None	None	None	N
L/E	0.9614	likely_pathogenic	0.9682	pathogenic	-0.672	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
L/F	0.63	likely_pathogenic	0.6661	pathogenic	-0.995	Destabilizing	0.998	D	0.686	prob.neutral	N	0.489390833	None	None	N
L/G	0.979	likely_pathogenic	0.98	pathogenic	-1.786	Destabilizing	0.991	D	0.716	prob.delet.	None	None	None	None	N
L/H	0.8468	likely_pathogenic	0.8579	pathogenic	-0.879	Destabilizing	0.998	D	0.685	prob.neutral	D	0.523522049	None	None	N
L/I	0.2182	likely_benign	0.2234	benign	-0.678	Destabilizing	0.979	D	0.459	neutral	N	0.430150528	None	None	N
L/K	0.8924	likely_pathogenic	0.9038	pathogenic	-0.873	Destabilizing	0.982	D	0.613	neutral	None	None	None	None	N
L/M	0.353	ambiguous	0.3742	ambiguous	-0.521	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
L/N	0.9424	likely_pathogenic	0.944	pathogenic	-0.69	Destabilizing	0.991	D	0.725	prob.delet.	None	None	None	None	N
L/P	0.977	likely_pathogenic	0.9724	pathogenic	-0.91	Destabilizing	0.998	D	0.73	prob.delet.	N	0.473775095	None	None	N
L/Q	0.7787	likely_pathogenic	0.7998	pathogenic	-0.847	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	N
L/R	0.8161	likely_pathogenic	0.8319	pathogenic	-0.289	Destabilizing	0.142	N	0.403	neutral	N	0.47970977	None	None	N
L/S	0.9492	likely_pathogenic	0.9526	pathogenic	-1.33	Destabilizing	0.991	D	0.708	prob.delet.	None	None	None	None	N
L/T	0.8813	likely_pathogenic	0.8972	pathogenic	-1.203	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
L/V	0.402	ambiguous	0.4194	ambiguous	-0.91	Destabilizing	0.979	D	0.445	neutral	N	0.454776827	None	None	N
L/W	0.8303	likely_pathogenic	0.8374	pathogenic	-1.044	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
L/Y	0.875	likely_pathogenic	0.8819	pathogenic	-0.819	Destabilizing	0.998	D	0.72	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.