TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18820	56683;56684;56685	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
N2AB	17179	51760;51761;51762	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
N2A	16252	48979;48980;48981	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
N2B	9755	29488;29489;29490	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
Novex-1	9880	29863;29864;29865	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
Novex-2	9947	30064;30065;30066	chr2:178599335;178599334;178599333	chr2:179464062;179464061;179464060
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-24
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1083
• 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
Y/H	rs2052657245	None	1.0	D	0.822	0.814	0.785519558449	gnomAD-4.0.0	1.60022E-06	None	None	None	None	N	None	0	0	None	0	2.79174E-05	None	0	0	0	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
Y/A	0.9971	likely_pathogenic	0.9949	pathogenic	-3.774	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/C	0.9407	likely_pathogenic	0.9108	pathogenic	-2.29	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.642118767	None	None	N
Y/D	0.9959	likely_pathogenic	0.9933	pathogenic	-3.989	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.642522375	None	None	N
Y/E	0.9992	likely_pathogenic	0.9986	pathogenic	-3.789	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.3228	likely_benign	0.2798	benign	-1.571	Destabilizing	0.999	D	0.65	neutral	D	0.552010316	None	None	N
Y/G	0.9924	likely_pathogenic	0.9882	pathogenic	-4.146	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
Y/H	0.9793	likely_pathogenic	0.9679	pathogenic	-2.852	Highly Destabilizing	1.0	D	0.822	deleterious	D	0.616580655	None	None	N
Y/I	0.9774	likely_pathogenic	0.9643	pathogenic	-2.498	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9978	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/L	0.9538	likely_pathogenic	0.937	pathogenic	-2.498	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
Y/M	0.9872	likely_pathogenic	0.9799	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/N	0.9838	likely_pathogenic	0.9761	pathogenic	-3.507	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.642522375	None	None	N
Y/P	0.9993	likely_pathogenic	0.9988	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
Y/Q	0.9986	likely_pathogenic	0.9977	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/R	0.9941	likely_pathogenic	0.9913	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/S	0.9905	likely_pathogenic	0.9845	pathogenic	-3.795	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.642522375	None	None	N
Y/T	0.9953	likely_pathogenic	0.9918	pathogenic	-3.488	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/V	0.9581	likely_pathogenic	0.9366	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
Y/W	0.8771	likely_pathogenic	0.8563	pathogenic	-0.837	Destabilizing	1.0	D	0.805	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.