TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1486	4681;4682;4683	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
N2AB	1486	4681;4682;4683	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
N2A	1486	4681;4682;4683	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
N2B	1440	4543;4544;4545	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
Novex-1	1440	4543;4544;4545	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
Novex-2	1440	4543;4544;4545	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453
Novex-3	1486	4681;4682;4683	chr2:178777728;178777727;178777726	chr2:179642455;179642454;179642453

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-6
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1958
• 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
P/L	None	None	1.0	D	0.831	0.716	0.835052448565	gnomAD-4.0.0	1.59079E-06	None	None	None	None	I	None	0	2.28676E-05	None	0	0	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
P/A	0.7771	likely_pathogenic	0.8459	pathogenic	-1.577	Destabilizing	1.0	D	0.783	deleterious	D	0.612406068	None	None	I
P/C	0.993	likely_pathogenic	0.9964	pathogenic	-1.122	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/D	0.9995	likely_pathogenic	0.9996	pathogenic	-2.333	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
P/E	0.998	likely_pathogenic	0.9986	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/F	0.9995	likely_pathogenic	0.9997	pathogenic	-1.372	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
P/G	0.986	likely_pathogenic	0.9902	pathogenic	-1.87	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
P/H	0.9988	likely_pathogenic	0.9992	pathogenic	-1.511	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/I	0.9913	likely_pathogenic	0.993	pathogenic	-0.861	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
P/K	0.9993	likely_pathogenic	0.9995	pathogenic	-1.305	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
P/L	0.9727	likely_pathogenic	0.9779	pathogenic	-0.861	Destabilizing	1.0	D	0.831	deleterious	D	0.680124808	None	None	I
P/M	0.9957	likely_pathogenic	0.9965	pathogenic	-0.626	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
P/N	0.9992	likely_pathogenic	0.9994	pathogenic	-1.191	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
P/Q	0.9974	likely_pathogenic	0.9981	pathogenic	-1.434	Destabilizing	1.0	D	0.841	deleterious	D	0.81682983	None	None	I
P/R	0.9977	likely_pathogenic	0.9983	pathogenic	-0.771	Destabilizing	1.0	D	0.835	deleterious	D	0.81682983	None	None	I
P/S	0.9866	likely_pathogenic	0.9906	pathogenic	-1.554	Destabilizing	1.0	D	0.838	deleterious	D	0.745755943	None	None	I
P/T	0.9777	likely_pathogenic	0.9834	pathogenic	-1.476	Destabilizing	1.0	D	0.84	deleterious	D	0.72414571	None	None	I
P/V	0.9612	likely_pathogenic	0.9723	pathogenic	-1.068	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.62	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
P/Y	0.9997	likely_pathogenic	0.9998	pathogenic	-1.319	Destabilizing	1.0	D	0.827	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.