TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26594	80005;80006;80007	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
N2AB	24953	75082;75083;75084	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
N2A	24026	72301;72302;72303	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
N2B	17529	52810;52811;52812	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
Novex-1	17654	53185;53186;53187	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
Novex-2	17721	53386;53387;53388	chr2:178566352;178566351;178566350	chr2:179431079;179431078;179431077
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: Ig-138
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.7992
• 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	rs759737599	-0.004	0.067	N	0.212	0.112	0.269558022972	gnomAD-2.1.1	5.63E-05	None	None	None	None	N	None	0	3.76702E-04	None	0	0	None	0	None	0	0	1.65618E-04
L/I	rs759737599	-0.004	0.067	N	0.212	0.112	0.269558022972	gnomAD-4.0.0	2.06916E-05	None	None	None	None	N	None	0	2.97265E-04	None	0	0	None	0	0	0	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	0.6976	likely_pathogenic	0.6779	pathogenic	-1.246	Destabilizing	0.968	D	0.623	neutral	None	None	None	None	N
L/C	0.8619	likely_pathogenic	0.8562	pathogenic	-0.923	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
L/D	0.9791	likely_pathogenic	0.9754	pathogenic	-0.347	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
L/E	0.921	likely_pathogenic	0.9133	pathogenic	-0.362	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
L/F	0.3762	ambiguous	0.3559	ambiguous	-0.874	Destabilizing	0.988	D	0.714	prob.delet.	N	0.49787569	None	None	N
L/G	0.932	likely_pathogenic	0.9164	pathogenic	-1.532	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	N
L/H	0.856	likely_pathogenic	0.8439	pathogenic	-0.749	Destabilizing	0.999	D	0.721	prob.delet.	D	0.534732991	None	None	N
L/I	0.0861	likely_benign	0.0756	benign	-0.557	Destabilizing	0.067	N	0.212	neutral	N	0.496101264	None	None	N
L/K	0.8715	likely_pathogenic	0.8604	pathogenic	-0.799	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
L/M	0.1655	likely_benign	0.1661	benign	-0.562	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
L/N	0.9102	likely_pathogenic	0.8925	pathogenic	-0.615	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
L/P	0.7614	likely_pathogenic	0.7547	pathogenic	-0.753	Destabilizing	0.998	D	0.734	prob.delet.	N	0.51202038	None	None	N
L/Q	0.7983	likely_pathogenic	0.7813	pathogenic	-0.748	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
L/R	0.8212	likely_pathogenic	0.818	pathogenic	-0.295	Destabilizing	0.998	D	0.716	prob.delet.	D	0.534479502	None	None	N
L/S	0.872	likely_pathogenic	0.8534	pathogenic	-1.237	Destabilizing	0.995	D	0.704	prob.neutral	None	None	None	None	N
L/T	0.563	ambiguous	0.5413	ambiguous	-1.124	Destabilizing	0.991	D	0.694	prob.neutral	None	None	None	None	N
L/V	0.1344	likely_benign	0.1532	benign	-0.753	Destabilizing	0.618	D	0.488	neutral	N	0.508218038	None	None	N
L/W	0.6934	likely_pathogenic	0.6848	pathogenic	-0.912	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
L/Y	0.8183	likely_pathogenic	0.8091	pathogenic	-0.681	Destabilizing	0.995	D	0.733	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.