TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3090	9493;9494;9495	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
N2AB	3090	9493;9494;9495	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
N2A	3090	9493;9494;9495	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
N2B	3044	9355;9356;9357	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
Novex-1	3044	9355;9356;9357	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
Novex-2	3044	9355;9356;9357	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776
Novex-3	3090	9493;9494;9495	chr2:178768051;178768050;178768049	chr2:179632778;179632777;179632776

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-21
• Domain position: 33
• Structural Position: 48
• Q(SASA): 0.1118
• 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
W/S	rs761150662	-3.112	0.971	D	0.852	0.899	0.952240869178	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
W/S	rs761150662	-3.112	0.971	D	0.852	0.899	0.952240869178	gnomAD-4.0.0	3.18109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86541E-05	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
W/A	0.9989	likely_pathogenic	0.9986	pathogenic	-2.831	Highly Destabilizing	0.86	D	0.832	deleterious	None	None	None	None	N
W/C	0.9995	likely_pathogenic	0.9993	pathogenic	-2.054	Highly Destabilizing	0.997	D	0.829	deleterious	D	0.756794634	None	None	N
W/D	0.9999	likely_pathogenic	0.9998	pathogenic	-3.48	Highly Destabilizing	0.993	D	0.861	deleterious	None	None	None	None	N
W/E	0.9998	likely_pathogenic	0.9997	pathogenic	-3.358	Highly Destabilizing	0.978	D	0.853	deleterious	None	None	None	None	N
W/F	0.8269	likely_pathogenic	0.8244	pathogenic	-1.835	Destabilizing	0.915	D	0.749	deleterious	None	None	None	None	N
W/G	0.9948	likely_pathogenic	0.9928	pathogenic	-3.077	Highly Destabilizing	0.971	D	0.813	deleterious	D	0.756845024	None	None	N
W/H	0.9992	likely_pathogenic	0.999	pathogenic	-2.296	Highly Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
W/I	0.9938	likely_pathogenic	0.9921	pathogenic	-1.899	Destabilizing	0.915	D	0.827	deleterious	None	None	None	None	N
W/K	0.9999	likely_pathogenic	0.9999	pathogenic	-2.908	Highly Destabilizing	0.978	D	0.853	deleterious	None	None	None	None	N
W/L	0.9783	likely_pathogenic	0.9747	pathogenic	-1.899	Destabilizing	0.014	N	0.715	prob.delet.	D	0.729473254	None	None	N
W/M	0.9961	likely_pathogenic	0.9958	pathogenic	-1.528	Destabilizing	0.956	D	0.771	deleterious	None	None	None	None	N
W/N	0.9998	likely_pathogenic	0.9997	pathogenic	-3.714	Highly Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
W/P	0.9998	likely_pathogenic	0.9996	pathogenic	-2.238	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
W/Q	0.9999	likely_pathogenic	0.9999	pathogenic	-3.443	Highly Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	N
W/R	0.9999	likely_pathogenic	0.9998	pathogenic	-2.832	Highly Destabilizing	0.971	D	0.853	deleterious	D	0.756794634	None	None	N
W/S	0.9992	likely_pathogenic	0.9988	pathogenic	-3.789	Highly Destabilizing	0.971	D	0.852	deleterious	D	0.756794634	None	None	N
W/T	0.9991	likely_pathogenic	0.9988	pathogenic	-3.591	Highly Destabilizing	0.956	D	0.809	deleterious	None	None	None	None	N
W/V	0.9951	likely_pathogenic	0.9936	pathogenic	-2.238	Highly Destabilizing	0.915	D	0.824	deleterious	None	None	None	None	N
W/Y	0.9635	likely_pathogenic	0.9622	pathogenic	-1.752	Destabilizing	0.978	D	0.748	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.