TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35326	106201;106202;106203	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
N2AB	33685	101278;101279;101280	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
N2A	32758	98497;98498;98499	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
N2B	26261	79006;79007;79008	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
Novex-1	26386	79381;79382;79383	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
Novex-2	26453	79582;79583;79584	chr2:178530639;178530638;178530637	chr2:179395366;179395365;179395364
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-165
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1314
• 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	None	None	1.0	D	0.862	0.81	0.767735741357	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	0.9041	likely_pathogenic	0.8743	pathogenic	-1.946	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
L/C	0.9383	likely_pathogenic	0.9172	pathogenic	-1.072	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9973	likely_pathogenic	0.9955	pathogenic	-1.967	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.9687	likely_pathogenic	0.9547	pathogenic	-1.726	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.6989	likely_pathogenic	0.5939	pathogenic	-1.207	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
L/G	0.9797	likely_pathogenic	0.9698	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/H	0.9641	likely_pathogenic	0.9408	pathogenic	-1.75	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/I	0.1825	likely_benign	0.1629	benign	-0.535	Destabilizing	0.813	D	0.318	neutral	None	None	None	None	N
L/K	0.9604	likely_pathogenic	0.9438	pathogenic	-1.258	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/M	0.3379	likely_benign	0.2887	benign	-0.506	Destabilizing	0.999	D	0.773	deleterious	N	0.506454654	None	None	N
L/N	0.9818	likely_pathogenic	0.9722	pathogenic	-1.707	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/P	0.9768	likely_pathogenic	0.9649	pathogenic	-0.989	Destabilizing	1.0	D	0.862	deleterious	D	0.543677122	None	None	N
L/Q	0.9105	likely_pathogenic	0.8741	pathogenic	-1.496	Destabilizing	1.0	D	0.839	deleterious	D	0.543930612	None	None	N
L/R	0.9349	likely_pathogenic	0.9103	pathogenic	-1.218	Destabilizing	1.0	D	0.845	deleterious	D	0.543677122	None	None	N
L/S	0.9817	likely_pathogenic	0.9703	pathogenic	-2.355	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/T	0.9237	likely_pathogenic	0.8934	pathogenic	-1.959	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/V	0.2709	likely_benign	0.2449	benign	-0.989	Destabilizing	0.981	D	0.489	neutral	D	0.524058846	None	None	N
L/W	0.9055	likely_pathogenic	0.8529	pathogenic	-1.462	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/Y	0.9434	likely_pathogenic	0.909	pathogenic	-1.134	Destabilizing	1.0	D	0.83	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.