TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14827	44704;44705;44706	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
N2AB	13186	39781;39782;39783	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
N2A	12259	37000;37001;37002	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
N2B	5762	17509;17510;17511	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
Novex-1	5887	17884;17885;17886	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
Novex-2	5954	18085;18086;18087	chr2:178625342;178625341;178625340	chr2:179490069;179490068;179490067
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-99
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.5481
• Predicted PPI site: I

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	None	None	0.999	N	0.395	0.134	0.29527378943	gnomAD-4.0.0	1.62002E-06	None	None	None	None	I	None	0	0	None	0	2.83624E-05	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	0.2998	likely_benign	0.3017	benign	-0.458	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	I
L/C	0.7911	likely_pathogenic	0.7664	pathogenic	-0.554	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
L/D	0.7775	likely_pathogenic	0.7748	pathogenic	-0.194	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/E	0.3861	ambiguous	0.4026	ambiguous	-0.3	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
L/F	0.311	likely_benign	0.3225	benign	-0.611	Destabilizing	1.0	D	0.639	neutral	D	0.550097352	None	None	I
L/G	0.6641	likely_pathogenic	0.6433	pathogenic	-0.59	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
L/H	0.4415	ambiguous	0.454	ambiguous	0.017	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
L/I	0.122	likely_benign	0.1283	benign	-0.242	Destabilizing	0.999	D	0.395	neutral	N	0.478053967	None	None	I
L/K	0.278	likely_benign	0.3083	benign	-0.256	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
L/M	0.1371	likely_benign	0.1369	benign	-0.341	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	I
L/N	0.5375	ambiguous	0.5449	ambiguous	-0.03	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
L/P	0.235	likely_benign	0.2274	benign	-0.282	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
L/Q	0.2302	likely_benign	0.2376	benign	-0.261	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/R	0.2622	likely_benign	0.27	benign	0.267	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
L/S	0.433	ambiguous	0.4307	ambiguous	-0.43	Destabilizing	1.0	D	0.705	prob.neutral	N	0.434092518	None	None	I
L/T	0.2496	likely_benign	0.2562	benign	-0.43	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
L/V	0.1332	likely_benign	0.137	benign	-0.282	Destabilizing	0.999	D	0.44	neutral	N	0.439958195	None	None	I
L/W	0.4488	ambiguous	0.4291	ambiguous	-0.642	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
L/Y	0.589	likely_pathogenic	0.5896	pathogenic	-0.376	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I

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.