TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21083	63472;63473;63474	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
N2AB	19442	58549;58550;58551	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
N2A	18515	55768;55769;55770	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
N2B	12018	36277;36278;36279	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
Novex-1	12143	36652;36653;36654	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
Novex-2	12210	36853;36854;36855	chr2:178588160;178588159;178588158	chr2:179452887;179452886;179452885
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: Fn3-41
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1063
• 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/P	rs2049444900	None	1.0	D	0.926	0.711	0.889011718437	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
L/P	rs2049444900	None	1.0	D	0.926	0.711	0.889011718437	gnomAD-4.0.0	6.57739E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07383E-04	0
L/R	None	None	1.0	D	0.897	0.694	0.857379640909	gnomAD-4.0.0	3.20812E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.77611E-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	0.807	likely_pathogenic	0.7778	pathogenic	-2.639	Highly Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
L/C	0.8502	likely_pathogenic	0.847	pathogenic	-1.499	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9989	pathogenic	-3.137	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/E	0.9932	likely_pathogenic	0.993	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/F	0.5071	ambiguous	0.5262	ambiguous	-1.584	Destabilizing	1.0	D	0.737	prob.delet.	D	0.523381053	None	None	N
L/G	0.9797	likely_pathogenic	0.9753	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.9851	likely_pathogenic	0.9861	pathogenic	-2.997	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.547779185	None	None	N
L/I	0.1284	likely_benign	0.1329	benign	-0.93	Destabilizing	0.999	D	0.547	neutral	N	0.469100606	None	None	N
L/K	0.9886	likely_pathogenic	0.9883	pathogenic	-1.942	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.2452	likely_benign	0.2469	benign	-1.128	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/N	0.995	likely_pathogenic	0.9941	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/P	0.9893	likely_pathogenic	0.9884	pathogenic	-1.496	Destabilizing	1.0	D	0.926	deleterious	D	0.547525695	None	None	N
L/Q	0.9786	likely_pathogenic	0.978	pathogenic	-2.291	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/R	0.9759	likely_pathogenic	0.976	pathogenic	-2.23	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.547525695	None	None	N
L/S	0.9807	likely_pathogenic	0.9787	pathogenic	-3.091	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/T	0.8767	likely_pathogenic	0.8481	pathogenic	-2.619	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/V	0.136	likely_benign	0.1379	benign	-1.496	Destabilizing	0.999	D	0.568	neutral	N	0.466930877	None	None	N
L/W	0.9479	likely_pathogenic	0.9553	pathogenic	-1.804	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.9652	likely_pathogenic	0.9666	pathogenic	-1.759	Destabilizing	1.0	D	0.823	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.