TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27570	82933;82934;82935	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
N2AB	25929	78010;78011;78012	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
N2A	25002	75229;75230;75231	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
N2B	18505	55738;55739;55740	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
Novex-1	18630	56113;56114;56115	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
Novex-2	18697	56314;56315;56316	chr2:178563424;178563423;178563422	chr2:179428151;179428150;179428149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-89
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.9182
• 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
P/L	rs1704409600	None	1.0	N	0.703	0.446	0.601121310199	gnomAD-4.0.0	1.59153E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85838E-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
P/A	0.122	likely_benign	0.1235	benign	-0.649	Destabilizing	0.999	D	0.72	deleterious	N	0.471690591	None	None	I
P/C	0.552	ambiguous	0.5497	ambiguous	-0.637	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/D	0.8932	likely_pathogenic	0.8795	pathogenic	-0.146	Destabilizing	1.0	D	0.723	deleterious	None	None	None	None	I
P/E	0.513	ambiguous	0.493	ambiguous	-0.254	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	I
P/F	0.7688	likely_pathogenic	0.7595	pathogenic	-0.853	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	I
P/G	0.641	likely_pathogenic	0.6363	pathogenic	-0.8	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
P/H	0.3784	ambiguous	0.3817	ambiguous	-0.354	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
P/I	0.3053	likely_benign	0.2789	benign	-0.399	Destabilizing	1.0	D	0.69	prob.delet.	None	None	None	None	I
P/K	0.2236	likely_benign	0.2423	benign	-0.359	Destabilizing	1.0	D	0.722	deleterious	None	None	None	None	I
P/L	0.1465	likely_benign	0.148	benign	-0.399	Destabilizing	1.0	D	0.703	prob.delet.	N	0.487250405	None	None	I
P/M	0.4073	ambiguous	0.3979	ambiguous	-0.292	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
P/N	0.7329	likely_pathogenic	0.7304	pathogenic	-0.085	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	I
P/Q	0.2218	likely_benign	0.2218	benign	-0.359	Destabilizing	1.0	D	0.703	prob.delet.	D	0.530855655	None	None	I
P/R	0.1703	likely_benign	0.1802	benign	0.14	Stabilizing	1.0	D	0.693	prob.delet.	N	0.493633187	None	None	I
P/S	0.2944	likely_benign	0.2929	benign	-0.538	Destabilizing	1.0	D	0.735	deleterious	N	0.50385063	None	None	I
P/T	0.1775	likely_benign	0.1833	benign	-0.544	Destabilizing	1.0	D	0.721	deleterious	D	0.529588208	None	None	I
P/V	0.1964	likely_benign	0.1754	benign	-0.447	Destabilizing	1.0	D	0.732	deleterious	None	None	None	None	I
P/W	0.8814	likely_pathogenic	0.8755	pathogenic	-0.894	Destabilizing	1.0	D	0.685	prob.delet.	None	None	None	None	I
P/Y	0.7392	likely_pathogenic	0.7385	pathogenic	-0.581	Destabilizing	1.0	D	0.705	prob.delet.	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.