TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27408	82447;82448;82449	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
N2AB	25767	77524;77525;77526	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
N2A	24840	74743;74744;74745	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
N2B	18343	55252;55253;55254	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
Novex-1	18468	55627;55628;55629	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
Novex-2	18535	55828;55829;55830	chr2:178563910;178563909;178563908	chr2:179428637;179428636;179428635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-87
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.1355
• 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
E/G	None	None	1.0	D	0.741	0.522	0.499473279415	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85866E-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
E/A	0.7406	likely_pathogenic	0.7217	pathogenic	-2.171	Highly Destabilizing	0.999	D	0.681	prob.neutral	D	0.547535241	None	None	N
E/C	0.9816	likely_pathogenic	0.9769	pathogenic	-1.22	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/D	0.7389	likely_pathogenic	0.6847	pathogenic	-1.727	Destabilizing	0.999	D	0.654	neutral	N	0.493475965	None	None	N
E/F	0.9881	likely_pathogenic	0.9845	pathogenic	-1.818	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/G	0.8298	likely_pathogenic	0.7963	pathogenic	-2.544	Highly Destabilizing	1.0	D	0.741	deleterious	D	0.531205413	None	None	N
E/H	0.9486	likely_pathogenic	0.9319	pathogenic	-1.646	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.9615	likely_pathogenic	0.9551	pathogenic	-1.083	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.8396	likely_pathogenic	0.8099	pathogenic	-2.044	Highly Destabilizing	0.999	D	0.68	prob.neutral	N	0.510059283	None	None	N
E/L	0.9406	likely_pathogenic	0.9259	pathogenic	-1.083	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/M	0.9148	likely_pathogenic	0.9007	pathogenic	-0.274	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.9185	likely_pathogenic	0.8943	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/P	0.9996	likely_pathogenic	0.9995	pathogenic	-1.436	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/Q	0.3076	likely_benign	0.2838	benign	-1.851	Destabilizing	1.0	D	0.759	deleterious	N	0.466925013	None	None	N
E/R	0.8957	likely_pathogenic	0.8789	pathogenic	-1.767	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/S	0.72	likely_pathogenic	0.6882	pathogenic	-2.878	Highly Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/T	0.8849	likely_pathogenic	0.8643	pathogenic	-2.522	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/V	0.894	likely_pathogenic	0.8746	pathogenic	-1.436	Destabilizing	1.0	D	0.732	prob.delet.	N	0.521797663	None	None	N
E/W	0.9941	likely_pathogenic	0.9919	pathogenic	-1.841	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9808	likely_pathogenic	0.9745	pathogenic	-1.659	Destabilizing	1.0	D	0.777	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.