TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14766	44521;44522;44523	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
N2AB	13125	39598;39599;39600	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
N2A	12198	36817;36818;36819	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
N2B	5701	17326;17327;17328	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
Novex-1	5826	17701;17702;17703	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
Novex-2	5893	17902;17903;17904	chr2:178629429;178629428;178629427	chr2:179494156;179494155;179494154
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-99
• Domain position: 2
• Structural Position: 3
• Q(SASA): 0.6316
• 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	0.483	0.321	0.643463202348	gnomAD-4.0.0	1.59344E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86246E-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	0.778	likely_pathogenic	0.8449	pathogenic	-1.401	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	I
L/C	0.8322	likely_pathogenic	0.8641	pathogenic	-0.808	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	I
L/D	0.9755	likely_pathogenic	0.9865	pathogenic	-0.585	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
L/E	0.8908	likely_pathogenic	0.9327	pathogenic	-0.519	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
L/F	0.4166	ambiguous	0.394	ambiguous	-0.755	Destabilizing	1.0	D	0.617	neutral	N	0.437437098	None	None	I
L/G	0.9367	likely_pathogenic	0.9576	pathogenic	-1.764	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
L/H	0.7784	likely_pathogenic	0.8443	pathogenic	-0.839	Destabilizing	1.0	D	0.736	prob.delet.	D	0.544525888	None	None	I
L/I	0.1515	likely_benign	0.1536	benign	-0.46	Destabilizing	0.999	D	0.483	neutral	N	0.427839842	None	None	I
L/K	0.7825	likely_pathogenic	0.8427	pathogenic	-0.832	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/M	0.25	likely_benign	0.2759	benign	-0.465	Destabilizing	1.0	D	0.588	neutral	None	None	None	None	I
L/N	0.8821	likely_pathogenic	0.9194	pathogenic	-0.822	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
L/P	0.7759	likely_pathogenic	0.8304	pathogenic	-0.743	Destabilizing	1.0	D	0.733	prob.delet.	D	0.544525888	None	None	I
L/Q	0.7005	likely_pathogenic	0.792	pathogenic	-0.866	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/R	0.7067	likely_pathogenic	0.7838	pathogenic	-0.388	Destabilizing	1.0	D	0.701	prob.neutral	D	0.54343115	None	None	I
L/S	0.8848	likely_pathogenic	0.9259	pathogenic	-1.496	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
L/T	0.7316	likely_pathogenic	0.8081	pathogenic	-1.298	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	I
L/V	0.1828	likely_benign	0.2101	benign	-0.743	Destabilizing	0.999	D	0.521	neutral	N	0.470256576	None	None	I
L/W	0.7216	likely_pathogenic	0.7501	pathogenic	-0.875	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
L/Y	0.8056	likely_pathogenic	0.8162	pathogenic	-0.607	Destabilizing	1.0	D	0.631	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.