TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8732	26419;26420;26421	chr2:178714992;178714991;178714990	chr2:179579719;179579718;179579717
N2AB	8415	25468;25469;25470	chr2:178714992;178714991;178714990	chr2:179579719;179579718;179579717
N2A	7488	22687;22688;22689	chr2:178714992;178714991;178714990	chr2:179579719;179579718;179579717
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-72
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.557
• 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/P	None	None	0.967	N	0.656	0.467	0.594679051289	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.2537	likely_benign	0.3699	ambiguous	-1.28	Destabilizing	0.473	N	0.482	neutral	None	None	None	None	I
L/C	0.4952	ambiguous	0.602	pathogenic	-0.85	Destabilizing	0.993	D	0.557	neutral	None	None	None	None	I
L/D	0.73	likely_pathogenic	0.8571	pathogenic	-0.624	Destabilizing	0.927	D	0.652	neutral	None	None	None	None	I
L/E	0.3597	ambiguous	0.5252	ambiguous	-0.635	Destabilizing	0.699	D	0.651	neutral	None	None	None	None	I
L/F	0.0982	likely_benign	0.1199	benign	-0.807	Destabilizing	0.654	D	0.478	neutral	N	0.496246942	None	None	I
L/G	0.5	ambiguous	0.6542	pathogenic	-1.574	Destabilizing	0.863	D	0.663	neutral	None	None	None	None	I
L/H	0.2543	likely_benign	0.3561	ambiguous	-0.688	Destabilizing	0.938	D	0.641	neutral	N	0.478582536	None	None	I
L/I	0.0934	likely_benign	0.1112	benign	-0.565	Destabilizing	0.02	N	0.419	neutral	N	0.478503757	None	None	I
L/K	0.2917	likely_benign	0.4048	ambiguous	-0.907	Destabilizing	0.085	N	0.566	neutral	None	None	None	None	I
L/M	0.1048	likely_benign	0.1112	benign	-0.543	Destabilizing	0.015	N	0.308	neutral	None	None	None	None	I
L/N	0.4622	ambiguous	0.595	pathogenic	-0.729	Destabilizing	0.927	D	0.645	neutral	None	None	None	None	I
L/P	0.2759	likely_benign	0.3788	ambiguous	-0.771	Destabilizing	0.967	D	0.656	neutral	N	0.478329046	None	None	I
L/Q	0.1531	likely_benign	0.22	benign	-0.888	Destabilizing	0.133	N	0.366	neutral	None	None	None	None	I
L/R	0.2153	likely_benign	0.3204	benign	-0.322	Destabilizing	0.654	D	0.61	neutral	N	0.478329046	None	None	I
L/S	0.2697	likely_benign	0.423	ambiguous	-1.316	Destabilizing	0.863	D	0.567	neutral	None	None	None	None	I
L/T	0.2498	likely_benign	0.3694	ambiguous	-1.207	Destabilizing	0.654	D	0.527	neutral	None	None	None	None	I
L/V	0.0945	likely_benign	0.1114	benign	-0.771	Destabilizing	0.026	N	0.443	neutral	N	0.441792729	None	None	I
L/W	0.1888	likely_benign	0.2551	benign	-0.849	Destabilizing	0.995	D	0.634	neutral	None	None	None	None	I
L/Y	0.3149	likely_benign	0.3795	ambiguous	-0.637	Destabilizing	0.373	N	0.533	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.