TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26903	80932;80933;80934	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
N2AB	25262	76009;76010;76011	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
N2A	24335	73228;73229;73230	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
N2B	17838	53737;53738;53739	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
Novex-1	17963	54112;54113;54114	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
Novex-2	18030	54313;54314;54315	chr2:178565425;178565424;178565423	chr2:179430152;179430151;179430150
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-139
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.2344
• 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
V/I	rs1559341049	None	None	N	0.289	0.151	0.409533910539	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66058E-04
V/I	rs1559341049	None	None	N	0.289	0.151	0.409533910539	gnomAD-4.0.0	4.79048E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49788E-06	1.15982E-05	1.65733E-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
V/A	0.4292	ambiguous	0.3845	ambiguous	-1.772	Destabilizing	0.052	N	0.625	neutral	N	0.488431693	None	None	I
V/C	0.7015	likely_pathogenic	0.6545	pathogenic	-1.604	Destabilizing	0.935	D	0.755	deleterious	None	None	None	None	I
V/D	0.9292	likely_pathogenic	0.9257	pathogenic	-1.859	Destabilizing	0.484	N	0.826	deleterious	D	0.60712442	None	None	I
V/E	0.8577	likely_pathogenic	0.8558	pathogenic	-1.775	Destabilizing	0.555	D	0.801	deleterious	None	None	None	None	I
V/F	0.1193	likely_benign	0.1106	benign	-1.268	Destabilizing	None	N	0.461	neutral	N	0.489633514	None	None	I
V/G	0.5755	likely_pathogenic	0.5437	ambiguous	-2.181	Highly Destabilizing	0.484	N	0.815	deleterious	D	0.581586308	None	None	I
V/H	0.8352	likely_pathogenic	0.8232	pathogenic	-1.814	Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	I
V/I	0.076	likely_benign	0.0733	benign	-0.702	Destabilizing	None	N	0.289	neutral	N	0.475230323	None	None	I
V/K	0.8422	likely_pathogenic	0.8444	pathogenic	-1.417	Destabilizing	0.555	D	0.8	deleterious	None	None	None	None	I
V/L	0.2184	likely_benign	0.2059	benign	-0.702	Destabilizing	0.004	N	0.485	neutral	D	0.56973676	None	None	I
V/M	0.191	likely_benign	0.1667	benign	-0.77	Destabilizing	0.38	N	0.669	neutral	None	None	None	None	I
V/N	0.7911	likely_pathogenic	0.7658	pathogenic	-1.409	Destabilizing	0.791	D	0.827	deleterious	None	None	None	None	I
V/P	0.9522	likely_pathogenic	0.9408	pathogenic	-1.026	Destabilizing	0.791	D	0.806	deleterious	None	None	None	None	I
V/Q	0.7865	likely_pathogenic	0.7802	pathogenic	-1.471	Destabilizing	0.791	D	0.797	deleterious	None	None	None	None	I
V/R	0.762	likely_pathogenic	0.772	pathogenic	-1.084	Destabilizing	0.555	D	0.829	deleterious	None	None	None	None	I
V/S	0.5953	likely_pathogenic	0.5503	ambiguous	-2.038	Highly Destabilizing	0.555	D	0.802	deleterious	None	None	None	None	I
V/T	0.5236	ambiguous	0.4773	ambiguous	-1.825	Destabilizing	0.149	N	0.66	neutral	None	None	None	None	I
V/W	0.835	likely_pathogenic	0.8175	pathogenic	-1.551	Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	I
V/Y	0.5335	ambiguous	0.5121	ambiguous	-1.217	Destabilizing	0.235	N	0.777	deleterious	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.