TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33654	101185;101186;101187	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
N2AB	32013	96262;96263;96264	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
N2A	31086	93481;93482;93483	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
N2B	24589	73990;73991;73992	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
Novex-1	24714	74365;74366;74367	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
Novex-2	24781	74566;74567;74568	chr2:178535655;178535654;178535653	chr2:179400382;179400381;179400380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-159
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1239
• 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
V/A	None	None	1.0	N	0.542	0.501	0.618519337204	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
V/A	0.8118	likely_pathogenic	0.6544	pathogenic	-1.909	Destabilizing	1.0	D	0.542	neutral	N	0.491631039	None	None	N
V/C	0.9472	likely_pathogenic	0.9076	pathogenic	-1.539	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/D	0.9686	likely_pathogenic	0.9119	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.786	deleterious	N	0.484251206	None	None	N
V/E	0.9241	likely_pathogenic	0.7998	pathogenic	-1.93	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/F	0.7282	likely_pathogenic	0.5234	ambiguous	-1.087	Destabilizing	1.0	D	0.769	deleterious	N	0.510201327	None	None	N
V/G	0.8803	likely_pathogenic	0.7914	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.747	deleterious	N	0.511002741	None	None	N
V/H	0.9626	likely_pathogenic	0.9108	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/I	0.1289	likely_benign	0.0995	benign	-0.522	Destabilizing	0.995	D	0.478	neutral	N	0.511489406	None	None	N
V/K	0.9549	likely_pathogenic	0.8796	pathogenic	-1.616	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/L	0.5438	ambiguous	0.3503	ambiguous	-0.522	Destabilizing	0.995	D	0.524	neutral	N	0.473491166	None	None	N
V/M	0.6105	likely_pathogenic	0.3967	ambiguous	-0.642	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
V/N	0.8857	likely_pathogenic	0.7753	pathogenic	-1.819	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/P	0.9964	likely_pathogenic	0.9941	pathogenic	-0.955	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/Q	0.8927	likely_pathogenic	0.7785	pathogenic	-1.702	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
V/R	0.9105	likely_pathogenic	0.813	pathogenic	-1.41	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/S	0.8096	likely_pathogenic	0.6781	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/T	0.6913	likely_pathogenic	0.5276	ambiguous	-2.152	Highly Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
V/W	0.9925	likely_pathogenic	0.9794	pathogenic	-1.526	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/Y	0.9422	likely_pathogenic	0.8809	pathogenic	-1.152	Destabilizing	1.0	D	0.777	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.