TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5298	16117;16118;16119	chr2:178733401;178733400;178733399	chr2:179598128;179598127;179598126
N2AB	4981	15166;15167;15168	chr2:178733401;178733400;178733399	chr2:179598128;179598127;179598126
N2A	4054	12385;12386;12387	chr2:178733401;178733400;178733399	chr2:179598128;179598127;179598126
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-36
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.4171
• 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
G/E	rs1395880212	-0.539	0.964	D	0.513	0.458	0.452928561435	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
G/E	rs1395880212	-0.539	0.964	D	0.513	0.458	0.452928561435	gnomAD-4.0.0	3.42103E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59789E-06	0	1.65656E-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
G/A	0.2994	likely_benign	0.3641	ambiguous	-0.334	Destabilizing	0.939	D	0.389	neutral	D	0.666446844	None	None	I
G/C	0.4147	ambiguous	0.4758	ambiguous	-0.867	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
G/D	0.2502	likely_benign	0.2815	benign	-0.56	Destabilizing	0.128	N	0.291	neutral	None	None	None	None	I
G/E	0.2948	likely_benign	0.344	ambiguous	-0.696	Destabilizing	0.964	D	0.513	neutral	D	0.628690807	None	None	I
G/F	0.8027	likely_pathogenic	0.8288	pathogenic	-0.92	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
G/H	0.4313	ambiguous	0.4745	ambiguous	-0.579	Destabilizing	0.998	D	0.565	neutral	None	None	None	None	I
G/I	0.6927	likely_pathogenic	0.7448	pathogenic	-0.358	Destabilizing	0.993	D	0.663	neutral	None	None	None	None	I
G/K	0.3934	ambiguous	0.4327	ambiguous	-0.911	Destabilizing	0.973	D	0.528	neutral	None	None	None	None	I
G/L	0.7159	likely_pathogenic	0.7685	pathogenic	-0.358	Destabilizing	0.986	D	0.659	neutral	None	None	None	None	I
G/M	0.7031	likely_pathogenic	0.756	pathogenic	-0.5	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	I
G/N	0.278	likely_benign	0.3125	benign	-0.559	Destabilizing	0.386	N	0.315	neutral	None	None	None	None	I
G/P	0.9827	likely_pathogenic	0.9889	pathogenic	-0.314	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	I
G/Q	0.3073	likely_benign	0.3498	ambiguous	-0.802	Destabilizing	0.986	D	0.565	neutral	None	None	None	None	I
G/R	0.2806	likely_benign	0.3138	benign	-0.475	Destabilizing	0.203	N	0.314	neutral	D	0.675207204	None	None	I
G/S	0.1336	likely_benign	0.1549	benign	-0.732	Destabilizing	0.953	D	0.423	neutral	None	None	None	None	I
G/T	0.3974	ambiguous	0.4702	ambiguous	-0.79	Destabilizing	0.986	D	0.538	neutral	None	None	None	None	I
G/V	0.5907	likely_pathogenic	0.657	pathogenic	-0.314	Destabilizing	0.991	D	0.655	neutral	D	0.76883003	None	None	I
G/W	0.6664	likely_pathogenic	0.697	pathogenic	-1.118	Destabilizing	0.999	D	0.611	neutral	D	0.736350434	None	None	I
G/Y	0.6597	likely_pathogenic	0.6878	pathogenic	-0.755	Destabilizing	0.999	D	0.659	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.